diff --git a/crates/uv-cli/src/lib.rs b/crates/uv-cli/src/lib.rs
index b6dfbf137..c100672bd 100644
--- a/crates/uv-cli/src/lib.rs
+++ b/crates/uv-cli/src/lib.rs
@@ -2617,6 +2617,12 @@ pub struct RunArgs {
     #[arg(long, conflicts_with("only_group"))]
     pub group: Vec<GroupName>,
 
+    /// Exclude dependencies from the specified local dependency group.
+    ///
+    /// May be provided multiple times.
+    #[arg(long)]
+    pub no_group: Vec<GroupName>,
+
     /// Only include dependencies from the specified local dependency group.
     ///
     /// May be provided multiple times.
@@ -2808,6 +2814,12 @@ pub struct SyncArgs {
     #[arg(long, conflicts_with("only_group"))]
     pub group: Vec<GroupName>,
 
+    /// Exclude dependencies from the specified local dependency group.
+    ///
+    /// May be provided multiple times.
+    #[arg(long)]
+    pub no_group: Vec<GroupName>,
+
     /// Only include dependencies from the specified local dependency group.
     ///
     /// May be provided multiple times.
@@ -3205,6 +3217,12 @@ pub struct TreeArgs {
     #[arg(long, conflicts_with("only_group"))]
     pub group: Vec<GroupName>,
 
+    /// Exclude dependencies from the specified local dependency group.
+    ///
+    /// May be provided multiple times.
+    #[arg(long)]
+    pub no_group: Vec<GroupName>,
+
     /// Only include dependencies from the specified local dependency group.
     ///
     /// May be provided multiple times.
@@ -3320,6 +3338,12 @@ pub struct ExportArgs {
     #[arg(long, conflicts_with("only_group"))]
     pub group: Vec<GroupName>,
 
+    /// Exclude dependencies from the specified local dependency group.
+    ///
+    /// May be provided multiple times.
+    #[arg(long)]
+    pub no_group: Vec<GroupName>,
+
     /// Only include dependencies from the specified local dependency group.
     ///
     /// May be provided multiple times.
diff --git a/crates/uv-configuration/src/dev.rs b/crates/uv-configuration/src/dev.rs
index 13a1f65d9..1c55eaa14 100644
--- a/crates/uv-configuration/src/dev.rs
+++ b/crates/uv-configuration/src/dev.rs
@@ -68,38 +68,76 @@ pub struct DevGroupsSpecification {
 #[derive(Debug, Clone)]
 pub enum GroupsSpecification {
     /// Include dependencies from the specified groups.
-    Include(Vec<GroupName>),
+    ///
+    /// The `include` list is guaranteed to omit groups in the `exclude` list (i.e., they have an
+    /// empty intersection).
+    Include {
+        include: Vec<GroupName>,
+        exclude: Vec<GroupName>,
+    },
     /// Only include dependencies from the specified groups, exclude all other dependencies.
-    Only(Vec<GroupName>),
+    ///
+    /// The `include` list is guaranteed to omit groups in the `exclude` list (i.e., they have an
+    /// empty intersection).
+    Only {
+        include: Vec<GroupName>,
+        exclude: Vec<GroupName>,
+    },
 }
 
 impl GroupsSpecification {
+    /// Create a [`GroupsSpecification`] that includes the given group.
+    pub fn from_group(group: GroupName) -> Self {
+        Self::Include {
+            include: vec![group],
+            exclude: Vec::new(),
+        }
+    }
+
     /// Returns `true` if the specification allows for production dependencies.
     pub fn prod(&self) -> bool {
-        matches!(self, Self::Include(_))
+        matches!(self, Self::Include { .. })
     }
 
     /// Returns `true` if the specification is limited to a select set of groups.
     pub fn only(&self) -> bool {
-        matches!(self, Self::Only(_))
+        matches!(self, Self::Only { .. })
     }
 
     /// Returns the option that was used to request the groups, if any.
     pub fn as_flag(&self) -> Option<Cow<'_, str>> {
         match self {
-            Self::Include(groups) => match groups.as_slice() {
-                [] => None,
+            Self::Include { include, exclude } => match include.as_slice() {
+                [] => match exclude.as_slice() {
+                    [] => None,
+                    [group] => Some(Cow::Owned(format!("--no-group {group}"))),
+                    [..] => Some(Cow::Borrowed("--no-group")),
+                },
                 [group] => Some(Cow::Owned(format!("--group {group}"))),
                 [..] => Some(Cow::Borrowed("--group")),
             },
-            Self::Only(groups) => match groups.as_slice() {
-                [] => None,
+            Self::Only { include, exclude } => match include.as_slice() {
+                [] => match exclude.as_slice() {
+                    [] => None,
+                    [group] => Some(Cow::Owned(format!("--no-group {group}"))),
+                    [..] => Some(Cow::Borrowed("--no-group")),
+                },
                 [group] => Some(Cow::Owned(format!("--only-group {group}"))),
                 [..] => Some(Cow::Borrowed("--only-group")),
             },
         }
     }
 
+    /// Iterate over all groups referenced in the [`DevGroupsSpecification`].
+    pub fn names(&self) -> impl Iterator<Item = &GroupName> {
+        match self {
+            GroupsSpecification::Include { include, exclude }
+            | GroupsSpecification::Only { include, exclude } => {
+                include.iter().chain(exclude.iter())
+            }
+        }
+    }
+
     /// Iterate over the group names to include.
     pub fn iter(&self) -> impl Iterator<Item = &GroupName> {
         <&Self as IntoIterator>::into_iter(self)
@@ -112,9 +150,14 @@ impl<'a> IntoIterator for &'a GroupsSpecification {
 
     fn into_iter(self) -> Self::IntoIter {
         match self {
-            GroupsSpecification::Include(groups) | GroupsSpecification::Only(groups) => {
-                groups.iter()
+            GroupsSpecification::Include {
+                include,
+                exclude: _,
             }
+            | GroupsSpecification::Only {
+                include,
+                exclude: _,
+            } => include.iter(),
         }
     }
 }
@@ -125,8 +168,9 @@ impl DevGroupsSpecification {
         dev: bool,
         no_dev: bool,
         only_dev: bool,
-        group: Vec<GroupName>,
-        only_group: Vec<GroupName>,
+        mut group: Vec<GroupName>,
+        no_group: Vec<GroupName>,
+        mut only_group: Vec<GroupName>,
     ) -> Self {
         let dev = if only_dev {
             Some(DevMode::Only)
@@ -142,12 +186,31 @@ impl DevGroupsSpecification {
             if matches!(dev, Some(DevMode::Only)) {
                 unreachable!("cannot specify both `--only-dev` and `--group`")
             };
-            Some(GroupsSpecification::Include(group))
+
+            // Ensure that `--no-group` and `--group` are mutually exclusive.
+            group.retain(|group| !no_group.contains(group));
+
+            Some(GroupsSpecification::Include {
+                include: group,
+                exclude: no_group,
+            })
         } else if !only_group.is_empty() {
             if matches!(dev, Some(DevMode::Include)) {
                 unreachable!("cannot specify both `--dev` and `--only-group`")
             };
-            Some(GroupsSpecification::Only(only_group))
+
+            // Ensure that `--no-group` and `--only-group` are mutually exclusive.
+            only_group.retain(|group| !no_group.contains(group));
+
+            Some(GroupsSpecification::Only {
+                include: only_group,
+                exclude: no_group,
+            })
+        } else if !no_group.is_empty() {
+            Some(GroupsSpecification::Include {
+                include: Vec::new(),
+                exclude: no_group,
+            })
         } else {
             None
         };
@@ -270,8 +333,24 @@ impl DevGroupsManifest {
                     .iter()
                     .chain(self.defaults.iter().filter(|default| {
                         // If `--no-dev` was provided, exclude the `dev` group from the list of defaults.
-                        !matches!(self.spec.dev_mode(), Some(DevMode::Exclude))
-                            || *default != &*DEV_DEPENDENCIES
+                        if matches!(self.spec.dev_mode(), Some(DevMode::Exclude)) {
+                            if *default == &*DEV_DEPENDENCIES {
+                                return false;
+                            };
+                        }
+
+                        // If `--no-group` was provided, exclude the group from the list of defaults.
+                        if let Some(GroupsSpecification::Include {
+                            include: _,
+                            exclude,
+                        }) = self.spec.groups()
+                        {
+                            if exclude.contains(default) {
+                                return false;
+                            }
+                        }
+
+                        true
                     })),
             )
         }
diff --git a/crates/uv/src/commands/project/add.rs b/crates/uv/src/commands/project/add.rs
index 20290a92b..772b03017 100644
--- a/crates/uv/src/commands/project/add.rs
+++ b/crates/uv/src/commands/project/add.rs
@@ -827,9 +827,7 @@ async fn lock_and_sync(
         DependencyType::Group(ref group_name) => {
             let extras = ExtrasSpecification::None;
             let dev =
-                DevGroupsSpecification::from(GroupsSpecification::Include(
-                    vec![group_name.clone()],
-                ));
+                DevGroupsSpecification::from(GroupsSpecification::from_group(group_name.clone()));
             (extras, dev)
         }
     };
diff --git a/crates/uv/src/commands/project/mod.rs b/crates/uv/src/commands/project/mod.rs
index 07fae6273..b6f8c53ef 100644
--- a/crates/uv/src/commands/project/mod.rs
+++ b/crates/uv/src/commands/project/mod.rs
@@ -8,8 +8,8 @@ use tracing::debug;
 use uv_cache::Cache;
 use uv_client::{BaseClientBuilder, Connectivity, FlatIndexClient, RegistryClientBuilder};
 use uv_configuration::{
-    Concurrency, Constraints, DevGroupsSpecification, ExtrasSpecification, LowerBound, Reinstall,
-    Upgrade,
+    Concurrency, Constraints, DevGroupsSpecification, ExtrasSpecification, GroupsSpecification,
+    LowerBound, Reinstall, Upgrade,
 };
 use uv_dispatch::BuildDispatch;
 use uv_distribution::DistributionDatabase;
@@ -1370,7 +1370,11 @@ pub(crate) fn validate_dependency_groups(
     pyproject_toml: &PyProjectToml,
     dev: &DevGroupsSpecification,
 ) -> Result<(), ProjectError> {
-    for group in dev.groups().into_iter().flatten() {
+    for group in dev
+        .groups()
+        .into_iter()
+        .flat_map(GroupsSpecification::names)
+    {
         if !pyproject_toml
             .dependency_groups
             .as_ref()
diff --git a/crates/uv/src/settings.rs b/crates/uv/src/settings.rs
index 6561dd27f..11237f6fc 100644
--- a/crates/uv/src/settings.rs
+++ b/crates/uv/src/settings.rs
@@ -253,6 +253,7 @@ impl RunSettings {
             dev,
             no_dev,
             group,
+            no_group,
             only_group,
             module: _,
             only_dev,
@@ -282,7 +283,9 @@ impl RunSettings {
                 flag(all_extras, no_all_extras).unwrap_or_default(),
                 extra.unwrap_or_default(),
             ),
-            dev: DevGroupsSpecification::from_args(dev, no_dev, only_dev, group, only_group),
+            dev: DevGroupsSpecification::from_args(
+                dev, no_dev, only_dev, group, no_group, only_group,
+            ),
             editable: EditableMode::from_args(no_editable),
             with,
             with_editable,
@@ -718,6 +721,7 @@ impl SyncSettings {
             only_dev,
             group,
             only_group,
+            no_group,
             no_editable,
             inexact,
             exact,
@@ -745,7 +749,9 @@ impl SyncSettings {
                 flag(all_extras, no_all_extras).unwrap_or_default(),
                 extra.unwrap_or_default(),
             ),
-            dev: DevGroupsSpecification::from_args(dev, no_dev, only_dev, group, only_group),
+            dev: DevGroupsSpecification::from_args(
+                dev, no_dev, only_dev, group, no_group, only_group,
+            ),
             editable: EditableMode::from_args(no_editable),
             install_options: InstallOptions::new(
                 no_install_project,
@@ -1028,6 +1034,7 @@ impl TreeSettings {
             only_dev,
             no_dev,
             group,
+            no_group,
             only_group,
             locked,
             frozen,
@@ -1039,7 +1046,9 @@ impl TreeSettings {
         } = args;
 
         Self {
-            dev: DevGroupsSpecification::from_args(dev, no_dev, only_dev, group, only_group),
+            dev: DevGroupsSpecification::from_args(
+                dev, no_dev, only_dev, group, no_group, only_group,
+            ),
             locked,
             frozen,
             universal,
@@ -1090,6 +1099,7 @@ impl ExportSettings {
             no_dev,
             only_dev,
             group,
+            no_group,
             only_group,
             header,
             no_header,
@@ -1115,7 +1125,9 @@ impl ExportSettings {
                 flag(all_extras, no_all_extras).unwrap_or_default(),
                 extra.unwrap_or_default(),
             ),
-            dev: DevGroupsSpecification::from_args(dev, no_dev, only_dev, group, only_group),
+            dev: DevGroupsSpecification::from_args(
+                dev, no_dev, only_dev, group, no_group, only_group,
+            ),
             editable: EditableMode::from_args(no_editable),
             hashes: flag(hashes, no_hashes).unwrap_or(true),
             install_options: InstallOptions::new(
diff --git a/crates/uv/tests/it/sync.rs b/crates/uv/tests/it/sync.rs
index 04ef7d210..baf0eeeba 100644
--- a/crates/uv/tests/it/sync.rs
+++ b/crates/uv/tests/it/sync.rs
@@ -1184,6 +1184,84 @@ fn sync_include_group() -> Result<()> {
     Ok(())
 }
 
+#[test]
+fn sync_exclude_group() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    let pyproject_toml = context.temp_dir.child("pyproject.toml");
+    pyproject_toml.write_str(
+        r#"
+        [project]
+        name = "project"
+        version = "0.1.0"
+        requires-python = ">=3.12"
+        dependencies = ["typing-extensions"]
+
+        [dependency-groups]
+        foo = ["anyio", {include-group = "bar"}]
+        bar = ["iniconfig"]
+        "#,
+    )?;
+
+    context.lock().assert().success();
+
+    uv_snapshot!(context.filters(), context.sync().arg("--group").arg("foo"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 6 packages in [TIME]
+    Prepared 5 packages in [TIME]
+    Installed 5 packages in [TIME]
+     + anyio==4.3.0
+     + idna==3.6
+     + iniconfig==2.0.0
+     + sniffio==1.3.1
+     + typing-extensions==4.10.0
+    "###);
+
+    uv_snapshot!(context.filters(), context.sync().arg("--group").arg("foo").arg("--no-group").arg("foo"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 6 packages in [TIME]
+    Uninstalled 4 packages in [TIME]
+     - anyio==4.3.0
+     - idna==3.6
+     - iniconfig==2.0.0
+     - sniffio==1.3.1
+    "###);
+
+    uv_snapshot!(context.filters(), context.sync().arg("--only-group").arg("bar"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 6 packages in [TIME]
+    Uninstalled 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + iniconfig==2.0.0
+     - typing-extensions==4.10.0
+    "###);
+
+    uv_snapshot!(context.filters(), context.sync().arg("--only-group").arg("bar").arg("--no-group").arg("bar"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 6 packages in [TIME]
+    Uninstalled 1 package in [TIME]
+     - iniconfig==2.0.0
+    "###);
+
+    Ok(())
+}
+
 #[test]
 fn sync_dev_group() -> Result<()> {
     let context = TestContext::new("3.12");
@@ -1257,6 +1335,15 @@ fn sync_non_existent_group() -> Result<()> {
     error: Group `baz` is not defined in the project's `dependency-group` table
     "###);
 
+    uv_snapshot!(context.filters(), context.sync().arg("--no-group").arg("baz"), @r###"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+
+    ----- stderr -----
+    error: Group `baz` is not defined in the project's `dependency-group` table
+    "###);
+
     // Requesting an empty group should succeed.
     uv_snapshot!(context.filters(), context.sync().arg("--group").arg("foo"), @r###"
     success: true
@@ -1407,6 +1494,38 @@ fn sync_default_groups() -> Result<()> {
      + sniffio==1.3.1
     "###);
 
+    // `--no-group` should remove from the defaults.
+    pyproject_toml.write_str(
+        r#"
+        [project]
+        name = "project"
+        version = "0.1.0"
+        requires-python = ">=3.12"
+        dependencies = ["typing-extensions"]
+
+        [dependency-groups]
+        dev = ["iniconfig"]
+        foo = ["anyio"]
+        bar = ["requests"]
+
+        [tool.uv]
+        default-groups = ["foo"]
+        "#,
+    )?;
+
+    uv_snapshot!(context.filters(), context.sync().arg("--no-group").arg("foo"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Resolved 10 packages in [TIME]
+    Uninstalled 3 packages in [TIME]
+     - anyio==4.3.0
+     - idna==3.6
+     - sniffio==1.3.1
+    "###);
+
     Ok(())
 }
 
diff --git a/docs/reference/cli.md b/docs/reference/cli.md
index 1046ccde5..9e5f9f93e 100644
--- a/docs/reference/cli.md
+++ b/docs/reference/cli.md
@@ -286,6 +286,10 @@ uv run [OPTIONS] [COMMAND]
 
 </dd><dt><code>--no-editable</code></dt><dd><p>Install any editable dependencies, including the project and any workspace members, as non-editable</p>
 
+</dd><dt><code>--no-group</code> <i>no-group</i></dt><dd><p>Exclude dependencies from the specified local dependency group.</p>
+
+<p>May be provided multiple times.</p>
+
 </dd><dt><code>--no-index</code></dt><dd><p>Ignore the registry index (e.g., PyPI), instead relying on direct URL dependencies and those provided via <code>--find-links</code></p>
 
 </dd><dt><code>--no-progress</code></dt><dd><p>Hide all progress outputs.</p>
@@ -1539,6 +1543,10 @@ uv sync [OPTIONS]
 
 </dd><dt><code>--no-editable</code></dt><dd><p>Install any editable dependencies, including the project and any workspace members, as non-editable</p>
 
+</dd><dt><code>--no-group</code> <i>no-group</i></dt><dd><p>Exclude dependencies from the specified local dependency group.</p>
+
+<p>May be provided multiple times.</p>
+
 </dd><dt><code>--no-index</code></dt><dd><p>Ignore the registry index (e.g., PyPI), instead relying on direct URL dependencies and those provided via <code>--find-links</code></p>
 
 </dd><dt><code>--no-install-package</code> <i>no-install-package</i></dt><dd><p>Do not install the given package(s).</p>
@@ -2189,6 +2197,10 @@ uv export [OPTIONS]
 
 <p>By default, all workspace members and their dependencies are included in the exported requirements file, with all of their dependencies. The <code>--no-emit-workspace</code> option allows exclusion of all the workspace members while retaining their dependencies.</p>
 
+</dd><dt><code>--no-group</code> <i>no-group</i></dt><dd><p>Exclude dependencies from the specified local dependency group.</p>
+
+<p>May be provided multiple times.</p>
+
 </dd><dt><code>--no-hashes</code></dt><dd><p>Omit hashes in the generated output</p>
 
 </dd><dt><code>--no-header</code></dt><dd><p>Exclude the comment header at the top of the generated output file</p>
@@ -2506,6 +2518,10 @@ uv tree [OPTIONS]
 
 </dd><dt><code>--no-dev</code></dt><dd><p>Omit development dependencies</p>
 
+</dd><dt><code>--no-group</code> <i>no-group</i></dt><dd><p>Exclude dependencies from the specified local dependency group.</p>
+
+<p>May be provided multiple times.</p>
+
 </dd><dt><code>--no-index</code></dt><dd><p>Ignore the registry index (e.g., PyPI), instead relying on direct URL dependencies and those provided via <code>--find-links</code></p>
 
 </dd><dt><code>--no-progress</code></dt><dd><p>Hide all progress outputs.</p>