diff --git a/.changeset/accept-header-not-acceptable.md b/.changeset/accept-header-not-acceptable.md
new file mode 100644
index 00000000000..4b4b90a2bbb
--- /dev/null
+++ b/.changeset/accept-header-not-acceptable.md
@@ -0,0 +1,5 @@
+---
+'@tanstack/start-server-core': patch
+---
+
+Return `406 Not Acceptable` instead of `500 Internal Server Error` when a page route receives a request whose `Accept` header excludes HTML.
diff --git a/e2e/react-start/basic/tests/accept-header.spec.ts b/e2e/react-start/basic/tests/accept-header.spec.ts
new file mode 100644
index 00000000000..b95c3b372dc
--- /dev/null
+++ b/e2e/react-start/basic/tests/accept-header.spec.ts
@@ -0,0 +1,30 @@
+import { expect } from '@playwright/test'
+import { test } from '@tanstack/router-e2e-utils'
+import { isPrerender } from './utils/isPrerender'
+import { isSpaMode } from './utils/isSpaMode'
+
+test.skip(
+  isSpaMode || isPrerender,
+  'Accept negotiation only runs when the document is server-rendered',
+)
+
+test.describe('Accept header negotiation', () => {
+  test('responds 406 when Accept excludes HTML', async ({ request }) => {
+    const response = await request.get('/', {
+      headers: { Accept: 'application/json' },
+    })
+
+    expect(response.status()).toBe(406)
+    expect(await response.json()).toEqual({
+      error: 'Only HTML requests are supported here',
+    })
+  })
+
+  test('responds 200 when Accept allows HTML', async ({ request }) => {
+    const response = await request.get('/', {
+      headers: { Accept: 'text/html' },
+    })
+
+    expect(response.status()).toBe(200)
+  })
+})
diff --git a/packages/start-server-core/src/createStartHandler.ts b/packages/start-server-core/src/createStartHandler.ts
index c7b427bfb1f..a9dc49c88c9 100644
--- a/packages/start-server-core/src/createStartHandler.ts
+++ b/packages/start-server-core/src/createStartHandler.ts
@@ -653,7 +653,7 @@ export function createStartHandler<TRegister = Register>(
           return normalizeSsrResponse(
             Response.json(
               { error: 'Only HTML requests are supported here' },
-              { status: 500 },
+              { status: 406 },
             ),
           )
         }