diff --git a/CHANGELOG.md b/CHANGELOG.md
index 73b0620facdf..0f8dce96de86 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -32,6 +32,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - [Oxide] Enable relative content paths for the `oxide` engine ([#10621](https://github.com/tailwindlabs/tailwindcss/pull/10621))
 - Mark `rtl` and `ltr` variants as stable and remove warnings ([#10764](https://github.com/tailwindlabs/tailwindcss/pull/10764))
 - Use `inset` instead of `top`, `right`, `bottom`, and `left` properties ([#10765](https://github.com/tailwindlabs/tailwindcss/pull/10765))
+- Make `dark` and `rtl`/`ltr` variants insensitive to DOM order ([#10766](https://github.com/tailwindlabs/tailwindcss/pull/10766))
 
 ## [3.2.7] - 2023-02-16
 
diff --git a/src/corePlugins.js b/src/corePlugins.js
index 4a97713fabe6..717c9ec5c350 100644
--- a/src/corePlugins.js
+++ b/src/corePlugins.js
@@ -199,8 +199,8 @@ export let variantPlugins = {
   },
 
   directionVariants: ({ addVariant }) => {
-    addVariant('ltr', '[dir="ltr"] &')
-    addVariant('rtl', '[dir="rtl"] &')
+    addVariant('ltr', ':is([dir="ltr"] &)')
+    addVariant('rtl', ':is([dir="rtl"] &)')
   },
 
   reducedMotionVariants: ({ addVariant }) => {
@@ -221,7 +221,7 @@ export let variantPlugins = {
     }
 
     if (mode === 'class') {
-      addVariant('dark', `${className} &`)
+      addVariant('dark', `:is(${className} &)`)
     } else if (mode === 'media') {
       addVariant('dark', '@media (prefers-color-scheme: dark)')
     }
diff --git a/tests/apply.test.js b/tests/apply.test.js
index cb5c6be068a6..14b84550a8a8 100644
--- a/tests/apply.test.js
+++ b/tests/apply.test.js
@@ -216,14 +216,14 @@ crosscheck(({ stable, oxide }) => {
             text-align: left;
           }
         }
-        .dark .apply-dark-variant {
+        :is(.dark .apply-dark-variant) {
           text-align: center;
         }
-        .dark .apply-dark-variant:hover {
+        :is(.dark .apply-dark-variant:hover) {
           text-align: right;
         }
         @media (min-width: 1024px) {
-          .dark .apply-dark-variant {
+          :is(.dark .apply-dark-variant) {
             text-align: left;
           }
         }
@@ -513,14 +513,14 @@ crosscheck(({ stable, oxide }) => {
             text-align: left;
           }
         }
-        .dark .apply-dark-variant {
+        :is(.dark .apply-dark-variant) {
           text-align: center;
         }
-        .dark .apply-dark-variant:hover {
+        :is(.dark .apply-dark-variant:hover) {
           text-align: right;
         }
         @media (min-width: 1024px) {
-          .dark .apply-dark-variant {
+          :is(.dark .apply-dark-variant) {
             text-align: left;
           }
         }
diff --git a/tests/custom-separator.test.js b/tests/custom-separator.test.js
index 8e788c5519ff..adc1d55afd65 100644
--- a/tests/custom-separator.test.js
+++ b/tests/custom-separator.test.js
@@ -23,7 +23,7 @@ crosscheck(() => {
         .group:hover .group-hover_focus-within_text-left:focus-within {
           text-align: left;
         }
-        [dir='rtl'] .rtl_active_text-center:active {
+        :is([dir='rtl'] .rtl_active_text-center:active) {
           text-align: center;
         }
         @media (prefers-reduced-motion: no-preference) {
@@ -31,7 +31,7 @@ crosscheck(() => {
             text-align: center;
           }
         }
-        .dark .dark_focus_text-left:focus {
+        :is(.dark .dark_focus_text-left:focus) {
           text-align: left;
         }
         @media (min-width: 768px) {
diff --git a/tests/dark-mode.test.js b/tests/dark-mode.test.js
index 2a1cbf43dd07..ce06496b2124 100644
--- a/tests/dark-mode.test.js
+++ b/tests/dark-mode.test.js
@@ -17,7 +17,7 @@ crosscheck(() => {
     return run(input, config).then((result) => {
       expect(result.css).toMatchFormattedCss(css`
         ${defaults}
-        .dark .dark\:font-bold {
+        :is(.dark .dark\:font-bold) {
           font-weight: 700;
         }
       `)
@@ -40,7 +40,7 @@ crosscheck(() => {
     return run(input, config).then((result) => {
       expect(result.css).toMatchFormattedCss(css`
         ${defaults}
-        .test-dark .dark\:font-bold {
+        :is(.test-dark .dark\:font-bold) {
           font-weight: 700;
         }
       `)
diff --git a/tests/important-boolean.test.js b/tests/important-boolean.test.js
index a7524e1f8fc1..895ca053c901 100644
--- a/tests/important-boolean.test.js
+++ b/tests/important-boolean.test.js
@@ -138,7 +138,7 @@ crosscheck(() => {
         .group:hover .group-hover\:focus-within\:text-left:focus-within {
           text-align: left !important;
         }
-        [dir='rtl'] .rtl\:active\:text-center:active {
+        :is([dir='rtl'] .rtl\:active\:text-center:active) {
           text-align: center !important;
         }
         @media (prefers-reduced-motion: no-preference) {
@@ -146,7 +146,7 @@ crosscheck(() => {
             text-align: center !important;
           }
         }
-        .dark .dark\:focus\:text-left:focus {
+        :is(.dark .dark\:focus\:text-left:focus) {
           text-align: left !important;
         }
         @media (min-width: 768px) {
diff --git a/tests/important-selector.test.js b/tests/important-selector.test.js
index cfa094342042..044037be1114 100644
--- a/tests/important-selector.test.js
+++ b/tests/important-selector.test.js
@@ -134,7 +134,7 @@ crosscheck(() => {
         #app .group:hover .group-hover\:focus-within\:text-left:focus-within {
           text-align: left;
         }
-        #app [dir='rtl'] .rtl\:active\:text-center:active {
+        #app :is([dir='rtl'] .rtl\:active\:text-center:active) {
           text-align: center;
         }
         @media (prefers-reduced-motion: no-preference) {
@@ -142,7 +142,7 @@ crosscheck(() => {
             text-align: center;
           }
         }
-        #app .dark .dark\:focus\:text-left:focus {
+        #app :is(.dark .dark\:focus\:text-left:focus) {
           text-align: left;
         }
         @media (min-width: 768px) {
diff --git a/tests/kitchen-sink.test.js b/tests/kitchen-sink.test.js
index d6d74225d293..a421e3a0b374 100644
--- a/tests/kitchen-sink.test.js
+++ b/tests/kitchen-sink.test.js
@@ -303,7 +303,7 @@ crosscheck(({ stable, oxide }) => {
         }
         .drop-empty-rules:hover,
         .group:hover .apply-group,
-        .dark .apply-dark-mode {
+        :is(.dark .apply-dark-mode) {
           font-weight: 700;
         }
         .apply-with-existing:hover {
@@ -338,7 +338,7 @@ crosscheck(({ stable, oxide }) => {
         .apply-order-b {
           margin: 1.5rem 1.25rem 1.25rem;
         }
-        .dark .group:hover .apply-dark-group-example-a {
+        :is(.dark .group:hover .apply-dark-group-example-a) {
           --tw-bg-opacity: 1;
           background-color: rgb(34 197 94 / var(--tw-bg-opacity));
         }
@@ -715,7 +715,7 @@ crosscheck(({ stable, oxide }) => {
             transition-timing-function: cubic-bezier(0.4, 0, 0.2, 1);
           }
         }
-        .dark .dark\:custom-util {
+        :is(.dark .dark\:custom-util) {
           background: #abcdef;
         }
         @media (min-width: 640px) {
@@ -762,7 +762,7 @@ crosscheck(({ stable, oxide }) => {
               transition-duration: 0.15s;
               transition-timing-function: cubic-bezier(0.4, 0, 0.2, 1);
             }
-            .dark .md\:dark\:motion-safe\:foo\:active\:custom-util:active {
+            :is(.dark .md\:dark\:motion-safe\:foo\:active\:custom-util:active) {
               background: #abcdef !important;
             }
           }
@@ -849,7 +849,7 @@ crosscheck(({ stable, oxide }) => {
         }
         .drop-empty-rules:hover,
         .group:hover .apply-group,
-        .dark .apply-dark-mode {
+        :is(.dark .apply-dark-mode) {
           font-weight: 700;
         }
         .apply-with-existing:hover {
@@ -883,7 +883,7 @@ crosscheck(({ stable, oxide }) => {
         .apply-order-b {
           margin: 1.5rem 1.25rem 1.25rem;
         }
-        .dark .group:hover .apply-dark-group-example-a {
+        :is(.dark .group:hover .apply-dark-group-example-a) {
           background-color: #22c55e;
         }
         @media (min-width: 640px) {
@@ -1250,7 +1250,7 @@ crosscheck(({ stable, oxide }) => {
             transition-timing-function: cubic-bezier(0.4, 0, 0.2, 1);
           }
         }
-        .dark .dark\:custom-util {
+        :is(.dark .dark\:custom-util) {
           background: #abcdef;
         }
         @media (min-width: 640px) {
@@ -1297,7 +1297,7 @@ crosscheck(({ stable, oxide }) => {
               transition-duration: 0.15s;
               transition-timing-function: cubic-bezier(0.4, 0, 0.2, 1);
             }
-            .dark .md\:dark\:motion-safe\:foo\:active\:custom-util:active {
+            :is(.dark .md\:dark\:motion-safe\:foo\:active\:custom-util:active) {
               background: #abcdef !important;
             }
           }
diff --git a/tests/prefix.test.js b/tests/prefix.test.js
index e0139ad9a979..ea3d041ffeac 100644
--- a/tests/prefix.test.js
+++ b/tests/prefix.test.js
@@ -128,7 +128,7 @@ crosscheck(({ stable, oxide }) => {
         .custom-component {
           font-weight: 700;
         }
-        .tw-dark .tw-group:hover .custom-component {
+        :is(.tw-dark .tw-group:hover .custom-component) {
           font-weight: 400;
         }
         .tw--ml-4 {
@@ -155,7 +155,7 @@ crosscheck(({ stable, oxide }) => {
         .tw-group:hover .group-hover\:focus-within\:tw-text-left:focus-within {
           text-align: left;
         }
-        [dir='rtl'] .rtl\:active\:tw-text-center:active {
+        :is([dir='rtl'] .rtl\:active\:tw-text-center:active) {
           text-align: center;
         }
         @media (prefers-reduced-motion: no-preference) {
@@ -163,11 +163,11 @@ crosscheck(({ stable, oxide }) => {
             text-align: center;
           }
         }
-        .tw-dark .dark\:tw-bg-\[rgb\(255\,0\,0\)\] {
+        :is(.tw-dark .dark\:tw-bg-\[rgb\(255\,0\,0\)\]) {
           --tw-bg-opacity: 1;
           background-color: rgb(255 0 0 / var(--tw-bg-opacity));
         }
-        .tw-dark .dark\:focus\:tw-text-left:focus {
+        :is(.tw-dark .dark\:focus\:tw-text-left:focus) {
           text-align: left;
         }
         @media (min-width: 768px) {
diff --git a/tests/variants.oxide.test.css b/tests/variants.oxide.test.css
index db3a5283f1a1..c2a490f4a805 100644
--- a/tests/variants.oxide.test.css
+++ b/tests/variants.oxide.test.css
@@ -283,8 +283,8 @@
 .peer:disabled ~ .peer-disabled\:shadow-md,
 .peer:disabled:focus:hover ~ .peer-disabled\:peer-focus\:peer-hover\:shadow-md,
 .peer:disabled:focus:hover ~ .peer-disabled\:peer-focus\:peer-hover\:first\:shadow-md:first-child,
-[dir="ltr"] .ltr\:shadow-md,
-[dir="rtl"] .rtl\:shadow-md {
+:is([dir='ltr'] .ltr\:shadow-md),
+:is([dir='rtl'] .rtl\:shadow-md) {
   --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
   --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color), 0 2px 4px -2px var(--tw-shadow-color);
   box-shadow: var(--tw-ring-offset-shadow, 0 0 #0000), var(--tw-ring-shadow, 0 0 #0000),
@@ -318,9 +318,9 @@
     background-color: #fde047;
   }
 }
-.dark .dark\:shadow-md,
-.dark .group:disabled:focus:hover .dark\:group-disabled\:group-focus\:group-hover\:shadow-md,
-.dark .peer:disabled:focus:hover ~ .dark\:peer-disabled\:peer-focus\:peer-hover\:shadow-md {
+:is(.dark .dark\:shadow-md),
+:is(.dark .group:disabled:focus:hover .dark\:group-disabled\:group-focus\:group-hover\:shadow-md),
+:is(.dark .peer:disabled:focus:hover ~ .dark\:peer-disabled\:peer-focus\:peer-hover\:shadow-md) {
   --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
   --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color), 0 2px 4px -2px var(--tw-shadow-color);
   box-shadow: var(--tw-ring-offset-shadow, 0 0 #0000), var(--tw-ring-shadow, 0 0 #0000),
@@ -361,7 +361,7 @@
     animation: 1s linear infinite spin;
   }
   .lg\:shadow-md,
-  .dark .lg\:dark\:shadow-md {
+  :is(.dark .lg\:dark\:shadow-md) {
     --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
     --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
       0 2px 4px -2px var(--tw-shadow-color);
@@ -371,7 +371,7 @@
 }
 @media (min-width: 1280px) {
   .xl\:shadow-md,
-  .dark .xl\:dark\:disabled\:shadow-md:disabled {
+  :is(.dark .xl\:dark\:disabled\:shadow-md:disabled) {
     --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
     --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
       0 2px 4px -2px var(--tw-shadow-color);
@@ -388,7 +388,7 @@
       var(--tw-shadow);
   }
   @media (prefers-reduced-motion: no-preference) {
-    .dark .\32 xl\:dark\:motion-safe\:focus-within\:shadow-md:focus-within {
+    :is(.dark .\32 xl\:dark\:motion-safe\:focus-within\:shadow-md:focus-within) {
       --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
       --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
         0 2px 4px -2px var(--tw-shadow-color);
@@ -407,4 +407,3 @@
     background-color: #fde047;
   }
 }
-
diff --git a/tests/variants.test.css b/tests/variants.test.css
index 7d0120d127a6..2f8181cf23c4 100644
--- a/tests/variants.test.css
+++ b/tests/variants.test.css
@@ -299,8 +299,8 @@
 .peer:disabled ~ .peer-disabled\:shadow-md,
 .peer:disabled:focus:hover ~ .peer-disabled\:peer-focus\:peer-hover\:shadow-md,
 .peer:disabled:focus:hover ~ .peer-disabled\:peer-focus\:peer-hover\:first\:shadow-md:first-child,
-[dir='ltr'] .ltr\:shadow-md,
-[dir='rtl'] .rtl\:shadow-md {
+:is([dir='ltr'] .ltr\:shadow-md),
+:is([dir='rtl'] .rtl\:shadow-md) {
   --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
   --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color), 0 2px 4px -2px var(--tw-shadow-color);
   box-shadow: var(--tw-ring-offset-shadow, 0 0 #0000), var(--tw-ring-shadow, 0 0 #0000),
@@ -336,9 +336,9 @@
     background-color: rgb(253 224 71 / var(--tw-bg-opacity));
   }
 }
-.dark .dark\:shadow-md,
-.dark .group:disabled:focus:hover .dark\:group-disabled\:group-focus\:group-hover\:shadow-md,
-.dark .peer:disabled:focus:hover ~ .dark\:peer-disabled\:peer-focus\:peer-hover\:shadow-md {
+:is(.dark .dark\:shadow-md),
+:is(.dark .group:disabled:focus:hover .dark\:group-disabled\:group-focus\:group-hover\:shadow-md),
+:is(.dark .peer:disabled:focus:hover ~ .dark\:peer-disabled\:peer-focus\:peer-hover\:shadow-md) {
   --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
   --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color), 0 2px 4px -2px var(--tw-shadow-color);
   box-shadow: var(--tw-ring-offset-shadow, 0 0 #0000), var(--tw-ring-shadow, 0 0 #0000),
@@ -380,7 +380,7 @@
     animation: 1s linear infinite spin;
   }
   .lg\:shadow-md,
-  .dark .lg\:dark\:shadow-md {
+  :is(.dark .lg\:dark\:shadow-md) {
     --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
     --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
       0 2px 4px -2px var(--tw-shadow-color);
@@ -390,7 +390,7 @@
 }
 @media (min-width: 1280px) {
   .xl\:shadow-md,
-  .dark .xl\:dark\:disabled\:shadow-md:disabled {
+  :is(.dark .xl\:dark\:disabled\:shadow-md:disabled) {
     --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
     --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
       0 2px 4px -2px var(--tw-shadow-color);
@@ -407,7 +407,7 @@
       var(--tw-shadow);
   }
   @media (prefers-reduced-motion: no-preference) {
-    .dark .\32 xl\:dark\:motion-safe\:focus-within\:shadow-md:focus-within {
+    :is(.dark .\32 xl\:dark\:motion-safe\:focus-within\:shadow-md:focus-within) {
       --tw-shadow: 0 4px 6px -1px #0000001a, 0 2px 4px -2px #0000001a;
       --tw-shadow-colored: 0 4px 6px -1px var(--tw-shadow-color),
         0 2px 4px -2px var(--tw-shadow-color);
diff --git a/tests/variants.test.js b/tests/variants.test.js
index a762745f082f..09c8ee538d08 100644
--- a/tests/variants.test.js
+++ b/tests/variants.test.js
@@ -1128,4 +1128,28 @@ crosscheck(({ stable, oxide }) => {
       }
     `)
   })
+
+  test('stacking dark and rtl variants', async () => {
+    let config = {
+      darkMode: 'class',
+      content: [
+        {
+          raw: html` <div class="dark:rtl:italic" /> `,
+        },
+      ],
+      corePlugins: { preflight: false },
+    }
+
+    let input = css`
+      @tailwind utilities;
+    `
+
+    let result = await run(input, config)
+
+    expect(result.css).toMatchFormattedCss(css`
+      :is(.dark :is([dir='rtl'] .dark\:rtl\:italic)) {
+        font-style: italic;
+      }
+    `)
+  })
 })