diff --git a/CHANGELOG.md b/CHANGELOG.md
index aa4fb368fc38..67deb410e402 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -22,6 +22,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - Skip over classes inside `:not(…)` when nested in an at-rule ([#12105](https://github.com/tailwindlabs/tailwindcss/pull/12105))
 - Update types to work with `Node16` module resolution ([#12097](https://github.com/tailwindlabs/tailwindcss/pull/12097))
 - Don’t crash when important and parent selectors are equal in `@apply` ([#12112](https://github.com/tailwindlabs/tailwindcss/pull/12112))
+- Eliminate irrelevant rules when applying variants ([#12113](https://github.com/tailwindlabs/tailwindcss/pull/12113))
 
 ### Added
 
diff --git a/src/lib/generateRules.js b/src/lib/generateRules.js
index a3418d6c6f25..da893f21a085 100644
--- a/src/lib/generateRules.js
+++ b/src/lib/generateRules.js
@@ -815,10 +815,19 @@ function applyFinalFormat(match, { context, candidate }) {
     }
 
     try {
-      rule.selector = finalizeSelector(rule.selector, finalFormat, {
+      let selector = finalizeSelector(rule.selector, finalFormat, {
         candidate,
         context,
       })
+
+      // Finalize Selector determined that this candidate is irrelevant
+      // TODO: This elimination should happen earlier so this never happens
+      if (selector === null) {
+        rule.remove()
+        return
+      }
+
+      rule.selector = selector
     } catch {
       // If this selector is invalid we also want to skip it
       // But it's likely that being invalid here means there's a bug in a plugin rather than too loosely matching content
diff --git a/src/util/formatVariantSelector.js b/src/util/formatVariantSelector.js
index bf8076183655..6ba6f2cb2b43 100644
--- a/src/util/formatVariantSelector.js
+++ b/src/util/formatVariantSelector.js
@@ -186,6 +186,13 @@ export function finalizeSelector(current, formats, { context, candidate, base })
   // Remove extraneous selectors that do not include the base candidate
   selector.each((sel) => eliminateIrrelevantSelectors(sel, base))
 
+  // If ffter eliminating irrelevant selectors, we end up with nothing
+  // Then the whole "rule" this is associated with does not need to exist
+  // We use `null` as a marker value for that case
+  if (selector.length === 0) {
+    return null
+  }
+
   // If there are no formats that means there were no variants added to the candidate
   // so we can just return the selector as-is
   let formatAst = Array.isArray(formats)
diff --git a/tests/basic-usage.test.js b/tests/basic-usage.test.js
index 2ac46990b972..1cc249d965fc 100644
--- a/tests/basic-usage.test.js
+++ b/tests/basic-usage.test.js
@@ -792,3 +792,46 @@ test('Skips classes inside :not() when nested inside an at-rule', async () => {
 
   expect(result.css).toMatchFormattedCss(css``)
 })
+
+test('Irrelevant rules are removed when applying variants', async () => {
+  let config = {
+    content: [
+      {
+        raw: html` <div class="md:w-full"></div> `,
+      },
+    ],
+    corePlugins: { preflight: false },
+    plugins: [
+      function ({ addUtilities }) {
+        addUtilities({
+          '@supports (foo: bar)': {
+            // This doesn't contain `w-full` so it should not exist in the output
+            '.outer': { color: 'red' },
+            '.outer:is(.w-full)': { color: 'green' },
+          },
+        })
+      },
+    ],
+  }
+
+  let input = css`
+    @tailwind utilities;
+  `
+
+  // We didn't find the hand class therefore
+  // nothing should be generated
+  let result = await run(input, config)
+
+  expect(result.css).toMatchFormattedCss(css`
+    @media (min-width: 768px) {
+      .md\:w-full {
+        width: 100%;
+      }
+      @supports (foo: bar) {
+        .outer.md\:w-full {
+          color: green;
+        }
+      }
+    }
+  `)
+})