diff --git a/crates/uv-python/src/version_files.rs b/crates/uv-python/src/version_files.rs
index 4067d1b4dd23..22cad953cd83 100644
--- a/crates/uv-python/src/version_files.rs
+++ b/crates/uv-python/src/version_files.rs
@@ -56,7 +56,17 @@ async fn read_versions_file() -> Result<Option<Vec<String>>, std::io::Error> {
     match fs::tokio::read_to_string(PYTHON_VERSIONS_FILENAME).await {
         Ok(content) => {
             debug!("Reading requests from `{PYTHON_VERSIONS_FILENAME}`");
-            Ok(Some(content.lines().map(ToString::to_string).collect()))
+            Ok(Some(
+                content
+                    .lines()
+                    .filter(|line| {
+                        // Skip comments and empty lines.
+                        let trimmed = line.trim();
+                        !(trimmed.is_empty() || trimmed.starts_with('#'))
+                    })
+                    .map(ToString::to_string)
+                    .collect(),
+            ))
         }
         Err(err) if err.kind() == std::io::ErrorKind::NotFound => Ok(None),
         Err(err) => Err(err),
@@ -67,7 +77,14 @@ async fn read_version_file() -> Result<Option<String>, std::io::Error> {
     match fs::tokio::read_to_string(PYTHON_VERSION_FILENAME).await {
         Ok(content) => {
             debug!("Reading requests from `{PYTHON_VERSION_FILENAME}`");
-            Ok(content.lines().next().map(ToString::to_string))
+            Ok(content
+                .lines()
+                .find(|line| {
+                    // Skip comments and empty lines.
+                    let trimmed = line.trim();
+                    !(trimmed.is_empty() || trimmed.starts_with('#'))
+                })
+                .map(ToString::to_string))
         }
         Err(err) if err.kind() == std::io::ErrorKind::NotFound => Ok(None),
         Err(err) => Err(err),
diff --git a/crates/uv/tests/python_pin.rs b/crates/uv/tests/python_pin.rs
index 32e3d36b3b76..3a08dc173899 100644
--- a/crates/uv/tests/python_pin.rs
+++ b/crates/uv/tests/python_pin.rs
@@ -1,11 +1,12 @@
 #![cfg(all(feature = "python", feature = "pypi"))]
 
-use assert_fs::fixture::{FileWriteStr as _, PathChild as _};
+use anyhow::Result;
+use assert_fs::fixture::{FileWriteStr, PathChild};
 use common::{uv_snapshot, TestContext};
 use insta::assert_snapshot;
 use uv_python::{
     platform::{Arch, Os},
-    PYTHON_VERSION_FILENAME,
+    PYTHON_VERSIONS_FILENAME, PYTHON_VERSION_FILENAME,
 };
 
 mod common;
@@ -629,3 +630,41 @@ fn python_pin_resolve() {
         "###);
     });
 }
+
+#[test]
+fn python_pin_with_comments() -> Result<()> {
+    let context = TestContext::new_with_versions(&[]);
+
+    let content = indoc::indoc! {r"
+        3.12
+
+        # 3.11
+        3.10
+    "};
+
+    let version_file = context.temp_dir.child(PYTHON_VERSION_FILENAME);
+    version_file.write_str(content)?;
+    uv_snapshot!(context.filters(), context.python_pin(), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+    3.12
+
+    ----- stderr -----
+    "###);
+    fs_err::remove_file(version_file)?;
+
+    let versions_file = context.temp_dir.child(PYTHON_VERSIONS_FILENAME);
+    versions_file.write_str(content)?;
+    uv_snapshot!(context.filters(), context.python_pin(), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+    3.12
+    3.10
+
+    ----- stderr -----
+    "###);
+
+    Ok(())
+}