diff --git a/core/modules/big_pipe/big_pipe.libraries.yml b/core/modules/big_pipe/big_pipe.libraries.yml
index f5774ef9750c..36d5f8e4dccc 100644
--- a/core/modules/big_pipe/big_pipe.libraries.yml
+++ b/core/modules/big_pipe/big_pipe.libraries.yml
@@ -5,6 +5,5 @@ big_pipe:
   drupalSettings:
     bigPipePlaceholderIds: []
   dependencies:
-    - core/once
     - core/drupal.ajax
     - core/drupalSettings
diff --git a/core/modules/big_pipe/js/big_pipe.js b/core/modules/big_pipe/js/big_pipe.js
index 097a036472d8..ea4f6f8cfb14 100644
--- a/core/modules/big_pipe/js/big_pipe.js
+++ b/core/modules/big_pipe/js/big_pipe.js
@@ -3,15 +3,39 @@
  * Renders BigPipe placeholders using Drupal's Ajax system.
  */
 
-(function (Drupal, drupalSettings) {
+((Drupal, drupalSettings) => {
   /**
-   * Maps textContent of <script type="application/vnd.drupal-ajax"> to an AJAX response.
+   * CSS selector for script elements to process on page load.
+   *
+   * @type {string}
+   */
+  const replacementsSelector = `script[data-big-pipe-replacement-for-placeholder-with-id]`;
+
+  /**
+   * Ajax object that will process all the BigPipe responses.
+   *
+   * Create a Drupal.Ajax object without associating an element, a progress
+   * indicator or a URL.
+   *
+   * @type {Drupal.Ajax}
+   */
+  const ajaxObject = Drupal.ajax({
+    url: '',
+    base: false,
+    element: false,
+    progress: false,
+  });
+
+  /**
+   * Maps textContent of <script type="application/vnd.drupal-ajax"> to an AJAX
+   * response.
    *
    * @param {string} content
-   *   The text content of a <script type="application/vnd.drupal-ajax"> DOM node.
+   *   The text content of a <script type="application/vnd.drupal-ajax"> DOM
+   *   node.
    * @return {Array|boolean}
-   *   The parsed Ajax response containing an array of Ajax commands, or false in
-   *   case the DOM node hasn't fully arrived yet.
+   *   The parsed Ajax response containing an array of Ajax commands, or false
+   *   in case the DOM node hasn't fully arrived yet.
    */
   function mapTextContentToAjaxResponse(content) {
     if (content === '') {
@@ -30,108 +54,85 @@
    *
    * These Ajax commands replace placeholders with HTML and load missing CSS/JS.
    *
-   * @param {HTMLScriptElement} placeholderReplacement
+   * @param {HTMLScriptElement} replacement
    *   Script tag created by BigPipe.
    */
-  function bigPipeProcessPlaceholderReplacement(placeholderReplacement) {
-    const placeholderId = placeholderReplacement.getAttribute(
-      'data-big-pipe-replacement-for-placeholder-with-id',
-    );
-    const content = placeholderReplacement.textContent.trim();
+  function processReplacement(replacement) {
+    const id = replacement.dataset.bigPipeReplacementForPlaceholderWithId;
+    // Because we use a mutation observer the content is guaranteed to be
+    // complete at this point.
+    const content = replacement.textContent.trim();
+
     // Ignore any placeholders that are not in the known placeholder list. Used
     // to avoid someone trying to XSS the site via the placeholdering mechanism.
-    if (
-      typeof drupalSettings.bigPipePlaceholderIds[placeholderId] !== 'undefined'
-    ) {
-      const response = mapTextContentToAjaxResponse(content);
-      // If we try to parse the content too early (when the JSON containing Ajax
-      // commands is still arriving), textContent will be empty or incomplete.
-      if (response === false) {
-        /**
-         * Mark as unprocessed so this will be retried later.
-         * @see bigPipeProcessDocument()
-         */
-        once.remove('big-pipe', placeholderReplacement);
-      } else {
-        // Create a Drupal.Ajax object without associating an element, a
-        // progress indicator or a URL.
-        const ajaxObject = Drupal.ajax({
-          url: '',
-          base: false,
-          element: false,
-          progress: false,
-        });
-        // Then, simulate an AJAX response having arrived, and let the Ajax
-        // system handle it.
-        ajaxObject.success(response, 'success');
-      }
+    if (typeof drupalSettings.bigPipePlaceholderIds[id] === 'undefined') {
+      return;
     }
+
+    // Immediately remove the replacement to prevent it being processed twice.
+    delete drupalSettings.bigPipePlaceholderIds[id];
+
+    const response = mapTextContentToAjaxResponse(content);
+
+    if (response === false) {
+      return;
+    }
+
+    // Then, simulate an AJAX response having arrived, and let the Ajax system
+    // handle it.
+    ajaxObject.success(response, 'success');
   }
 
-  // The frequency with which to check for newly arrived BigPipe placeholders.
-  // Hence 50 ms means we check 20 times per second. Setting this to 100 ms or
-  // more would cause the user to see content appear noticeably slower.
-  const interval = drupalSettings.bigPipeInterval || 50;
-
-  // The internal ID to contain the watcher service.
-  let timeoutID;
-
   /**
-   * Processes a streamed HTML document receiving placeholder replacements.
+   * Check that the element is valid to process and process it.
    *
-   * @param {HTMLDocument} context
-   *   The HTML document containing <script type="application/vnd.drupal-ajax">
-   *   tags generated by BigPipe.
-   *
-   * @return {bool}
-   *   Returns true when processing has been finished and a stop signal has been
-   *   found.
+   * @param {HTMLElement} node
+   *  The node added to the body element.
    */
-  function bigPipeProcessDocument(context) {
-    // Make sure we have BigPipe-related scripts before processing further.
-    if (!context.querySelector('script[data-big-pipe-event="start"]')) {
-      return false;
+  function checkMutationAndProcess(node) {
+    if (
+      node.nodeType === Node.ELEMENT_NODE &&
+      node.nodeName === 'SCRIPT' &&
+      node.dataset &&
+      node.dataset.bigPipeReplacementForPlaceholderWithId
+    ) {
+      processReplacement(node);
     }
+  }
 
-    // Attach Drupal behaviors early, if possible.
-    once('big-pipe-early-behaviors', 'body', context).forEach((el) => {
-      Drupal.attachBehaviors(el);
+  /**
+   * Handles the mutation callback.
+   *
+   * @param {MutationRecord[]} mutations
+   *  The list of mutations registered by the browser.
+   */
+  function processMutations(mutations) {
+    mutations.forEach(({ addedNodes }) => {
+      addedNodes.forEach(checkMutationAndProcess);
     });
-
-    once(
-      'big-pipe',
-      'script[data-big-pipe-replacement-for-placeholder-with-id]',
-      context,
-    ).forEach(bigPipeProcessPlaceholderReplacement);
-
-    // If we see the stop signal, clear the timeout: all placeholder
-    // replacements are guaranteed to be received and processed.
-    if (context.querySelector('script[data-big-pipe-event="stop"]')) {
-      if (timeoutID) {
-        clearTimeout(timeoutID);
-      }
-      return true;
-    }
-
-    return false;
   }
 
-  function bigPipeProcess() {
-    timeoutID = setTimeout(() => {
-      if (!bigPipeProcessDocument(document)) {
-        bigPipeProcess();
-      }
-    }, interval);
-  }
+  const observer = new MutationObserver(processMutations);
 
-  bigPipeProcess();
+  // Attach behaviors early, if possible.
+  Drupal.attachBehaviors(document.body);
 
-  // If something goes wrong, make sure everything is cleaned up and has had a
-  // chance to be processed with everything loaded.
-  window.addEventListener('load', () => {
-    if (timeoutID) {
-      clearTimeout(timeoutID);
+  // If loaded asynchronously there might already be replacement elements
+  // in the DOM before the mutation observer is started.
+  document.querySelectorAll(replacementsSelector).forEach(processReplacement);
+
+  // Start observing the body element for new children.
+  observer.observe(document.body, { childList: true });
+
+  // As soon as the document is loaded, no more replacements will be added.
+  // Immediately fetch and process all pending mutations and stop the observer.
+  window.addEventListener('DOMContentLoaded', () => {
+    const mutations = observer.takeRecords();
+    observer.disconnect();
+    if (mutations.length) {
+      processMutations(mutations);
     }
-    bigPipeProcessDocument(document);
+    // No more mutations will be processed, remove the leftover Ajax object.
+    Drupal.ajax.instances[ajaxObject.instanceIndex] = null;
   });
 })(Drupal, drupalSettings);
diff --git a/core/modules/ckeditor5/js/ckeditor5.admin.js b/core/modules/ckeditor5/js/ckeditor5.admin.js
index c996d2f506f1..5368736f4dfd 100644
--- a/core/modules/ckeditor5/js/ckeditor5.admin.js
+++ b/core/modules/ckeditor5/js/ckeditor5.admin.js
@@ -530,69 +530,71 @@
    */
   Drupal.behaviors.ckeditor5Admin = {
     attach(context) {
-      once('ckeditor5-admin-toolbar', '#ckeditor5-toolbar-app').forEach(
-        (container) => {
-          const selectedTextarea = context.querySelector(
-            '#ckeditor5-toolbar-buttons-selected',
-          );
-          const available = Object.entries(
-            JSON.parse(
-              context.querySelector('#ckeditor5-toolbar-buttons-available')
-                .innerHTML,
-            ),
-          ).map(([name, attrs]) => ({ name, id: name, ...attrs }));
-          const dividers = [
-            {
-              id: 'divider',
-              name: '|',
-              label: Drupal.t('Divider'),
-            },
-            {
-              id: 'wrapping',
-              name: '-',
-              label: Drupal.t('Wrapping'),
-            },
-          ];
+      once(
+        'ckeditor5-admin-toolbar',
+        '#ckeditor5-toolbar-app',
+        context,
+      ).forEach((container) => {
+        const selectedTextarea = context.querySelector(
+          '#ckeditor5-toolbar-buttons-selected',
+        );
+        const available = Object.entries(
+          JSON.parse(
+            context.querySelector('#ckeditor5-toolbar-buttons-available')
+              .innerHTML,
+          ),
+        ).map(([name, attrs]) => ({ name, id: name, ...attrs }));
+        const dividers = [
+          {
+            id: 'divider',
+            name: '|',
+            label: Drupal.t('Divider'),
+          },
+          {
+            id: 'wrapping',
+            name: '-',
+            label: Drupal.t('Wrapping'),
+          },
+        ];
 
-          // Selected is used for managing the state. Sortable is handling updates
-          // to the state when the system is operated by mouse. There are
-          // functions making direct modifications to the state when system is
-          // operated by keyboard.
-          const selected = new Observable(
-            JSON.parse(selectedTextarea.innerHTML).map((name) => {
-              return [...dividers, ...available].find((button) => {
-                return button.name === name;
-              }).id;
-            }),
-          );
+        // Selected is used for managing the state. Sortable is handling updates
+        // to the state when the system is operated by mouse. There are
+        // functions making direct modifications to the state when system is
+        // operated by keyboard.
+        const selected = new Observable(
+          JSON.parse(selectedTextarea.innerHTML).map((name) => {
+            return [...dividers, ...available].find((button) => {
+              return button.name === name;
+            }).id;
+          }),
+        );
 
-          const mapSelection = (selection) => {
-            return selection.map((id) => {
-              return [...dividers, ...available].find((button) => {
-                return button.id === id;
-              }).name;
-            });
-          };
-          // Whenever the state is changed, update the textarea with the changes.
-          // This will also trigger re-render of the admin UI to reinitialize the
-          // Sortable state.
-          selected.subscribe((selection) => {
-            updateSelectedButtons(mapSelection(selection), selectedTextarea);
-            render(container, selected, available, dividers);
+        const mapSelection = (selection) => {
+          return selection.map((id) => {
+            return [...dividers, ...available].find((button) => {
+              return button.id === id;
+            }).name;
+          });
+        };
+        // Whenever the state is changed, update the textarea with the changes.
+        // This will also trigger re-render of the admin UI to reinitialize the
+        // Sortable state.
+        selected.subscribe((selection) => {
+          updateSelectedButtons(mapSelection(selection), selectedTextarea);
+          render(container, selected, available, dividers);
+        });
+
+        [
+          context.querySelector('#ckeditor5-toolbar-buttons-available'),
+          context.querySelector('[class*="editor-settings-toolbar-items"]'),
+        ]
+          .filter((el) => el)
+          .forEach((el) => {
+            el.classList.add('visually-hidden');
           });
 
-          [
-            context.querySelector('#ckeditor5-toolbar-buttons-available'),
-            context.querySelector('[class*="editor-settings-toolbar-items"]'),
-          ]
-            .filter((el) => el)
-            .forEach((el) => {
-              el.classList.add('visually-hidden');
-            });
-
-          render(container, selected, available, dividers);
-        },
-      );
+        render(container, selected, available, dividers);
+      });
       // Safari's focus outlines take into account absolute positioned elements.
       // When a toolbar option is blurred, the portion of the focus outline
       // surrounding the absolutely positioned tooltip does not go away. To
diff --git a/core/profiles/standard/tests/src/FunctionalJavascript/StandardJavascriptTest.php b/core/profiles/standard/tests/src/FunctionalJavascript/StandardJavascriptTest.php
index cec79deacf50..7f4bf7985670 100644
--- a/core/profiles/standard/tests/src/FunctionalJavascript/StandardJavascriptTest.php
+++ b/core/profiles/standard/tests/src/FunctionalJavascript/StandardJavascriptTest.php
@@ -54,7 +54,8 @@ class StandardJavascriptTest extends WebDriverTestBase {
     $web_assert = $this->assertSession();
     $web_assert->waitForElement('css', 'script[data-big-pipe-event="stop"]');
     $page = $this->getSession()->getPage();
-    $this->assertCount($expected_count, $this->getDrupalSettings()['bigPipePlaceholderIds']);
+    // Settings are removed as soon as they are processed.
+    $this->assertCount(0, $this->getDrupalSettings()['bigPipePlaceholderIds']);
     $this->assertCount($expected_count, $page->findAll('css', 'script[data-big-pipe-replacement-for-placeholder-with-id]'));
   }