diff --git a/crates/uv-cli/src/lib.rs b/crates/uv-cli/src/lib.rs
index c9e92ded3157..b4b0a176a47b 100644
--- a/crates/uv-cli/src/lib.rs
+++ b/crates/uv-cli/src/lib.rs
@@ -2472,7 +2472,7 @@ pub struct RunArgs {
     /// Run a Python module.
     ///
     /// Equivalent to `python -m <module>`.
-    #[arg(short, long)]
+    #[arg(short, long, conflicts_with = "script")]
     pub module: bool,
 
     /// Omit non-development dependencies.
@@ -2554,6 +2554,13 @@ pub struct RunArgs {
     #[arg(long, conflicts_with = "locked")]
     pub frozen: bool,
 
+    /// Run the given path as a Python script.
+    ///
+    /// Using `--script` will attempt to parse the path as a PEP 723 script,
+    /// irrespective of its extension.
+    #[arg(long, short, conflicts_with = "module")]
+    pub script: bool,
+
     #[command(flatten)]
     pub installer: ResolverInstallerArgs,
 
diff --git a/crates/uv/src/commands/project/run.rs b/crates/uv/src/commands/project/run.rs
index d6b0dadc039c..d6c94592c9d7 100644
--- a/crates/uv/src/commands/project/run.rs
+++ b/crates/uv/src/commands/project/run.rs
@@ -1021,7 +1021,11 @@ impl std::fmt::Display for RunCommand {
 }
 
 impl RunCommand {
-    pub(crate) fn from_args(command: &ExternalCommand, module: bool) -> anyhow::Result<Self> {
+    pub(crate) fn from_args(
+        command: &ExternalCommand,
+        module: bool,
+        script: bool,
+    ) -> anyhow::Result<Self> {
         let (target, args) = command.split();
         let Some(target) = target else {
             return Ok(Self::Empty);
@@ -1029,6 +1033,8 @@ impl RunCommand {
 
         if module {
             return Ok(Self::PythonModule(target.clone(), args.to_vec()));
+        } else if script {
+            return Ok(Self::PythonScript(target.clone().into(), args.to_vec()));
         }
 
         let target_path = PathBuf::from(target);
diff --git a/crates/uv/src/lib.rs b/crates/uv/src/lib.rs
index 7eb87fcae77c..4e236d470ebd 100644
--- a/crates/uv/src/lib.rs
+++ b/crates/uv/src/lib.rs
@@ -132,10 +132,13 @@ async fn run(cli: Cli) -> Result<ExitStatus> {
     // Parse the external command, if necessary.
     let run_command = if let Commands::Project(command) = &*cli.command {
         if let ProjectCommand::Run(uv_cli::RunArgs {
-            command, module, ..
+            command,
+            module,
+            script,
+            ..
         }) = &**command
         {
-            Some(RunCommand::from_args(command, *module)?)
+            Some(RunCommand::from_args(command, *module, *script)?)
         } else {
             None
         }
diff --git a/crates/uv/src/settings.rs b/crates/uv/src/settings.rs
index 55a372a45385..582e20787cc6 100644
--- a/crates/uv/src/settings.rs
+++ b/crates/uv/src/settings.rs
@@ -248,6 +248,7 @@ impl RunSettings {
             module: _,
             only_dev,
             no_editable,
+            script: _,
             command: _,
             with,
             with_editable,
diff --git a/crates/uv/tests/run.rs b/crates/uv/tests/run.rs
index 645e495927c9..dd9751e2a8a5 100644
--- a/crates/uv/tests/run.rs
+++ b/crates/uv/tests/run.rs
@@ -5,6 +5,7 @@ use anyhow::Result;
 use assert_cmd::assert::OutputAssertExt;
 use assert_fs::{fixture::ChildPath, prelude::*};
 use indoc::indoc;
+use predicates::str::contains;
 use std::path::Path;
 
 use uv_python::PYTHON_VERSION_FILENAME;
@@ -2164,3 +2165,69 @@ fn run_script_without_build_system() -> Result<()> {
 
     Ok(())
 }
+
+#[test]
+fn run_script_explicit() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    let test_script = context.temp_dir.child("script");
+    test_script.write_str(indoc! { r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = [
+        #   "iniconfig",
+        # ]
+        # ///
+        import iniconfig
+        print("Hello, world!")
+       "#
+    })?;
+
+    uv_snapshot!(context.filters(), context.run().arg("--script").arg("script"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+    Hello, world!
+
+    ----- stderr -----
+    Reading inline script metadata from: script
+    Resolved 1 package in [TIME]
+    Prepared 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + iniconfig==2.0.0
+    "###);
+
+    Ok(())
+}
+
+#[test]
+fn run_script_explicit_no_file() {
+    let context = TestContext::new("3.12");
+    context
+        .run()
+        .arg("--script")
+        .arg("script")
+        .assert()
+        .stderr(contains("can't open file"))
+        .stderr(contains("[Errno 2] No such file or directory"));
+}
+
+#[cfg(target_family = "unix")]
+#[test]
+fn run_script_explicit_directory() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    fs_err::create_dir(context.temp_dir.child("script"))?;
+
+    uv_snapshot!(context.filters(), context.run().arg("--script").arg("script"), @r###"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+
+    ----- stderr -----
+    error: failed to read from file `script`
+      Caused by: Is a directory (os error 21)
+    "###);
+
+    Ok(())
+}
diff --git a/docs/reference/cli.md b/docs/reference/cli.md
index 4b0c56f3071c..83292120a0fe 100644
--- a/docs/reference/cli.md
+++ b/docs/reference/cli.md
@@ -371,6 +371,10 @@ uv run [OPTIONS] <COMMAND>
 
 <li><code>lowest-direct</code>:  Resolve the lowest compatible version of any direct dependencies, and the highest compatible version of any transitive dependencies</li>
 </ul>
+</dd><dt><code>--script</code>, <code>-s</code></dt><dd><p>Run the given path as a Python script.</p>
+
+<p>Using <code>--script</code> will attempt to parse the path as a PEP 723 script, irrespective of its extension.</p>
+
 </dd><dt><code>--upgrade</code>, <code>-U</code></dt><dd><p>Allow package upgrades, ignoring pinned versions in any existing output file. Implies <code>--refresh</code></p>
 
 </dd><dt><code>--upgrade-package</code>, <code>-P</code> <i>upgrade-package</i></dt><dd><p>Allow upgrades for a specific package, ignoring pinned versions in any existing output file. Implies <code>--refresh-package</code></p>