diff --git a/browser/components/originattributes/test/browser/browser_cache.js b/browser/components/originattributes/test/browser/browser_cache.js
index f1d380cd31fa..9acb0743ad74 100644
--- a/browser/components/originattributes/test/browser/browser_cache.js
+++ b/browser/components/originattributes/test/browser/browser_cache.js
@@ -151,6 +151,7 @@ async function doInit(aMode) {
     set: [
       ["network.predictor.enabled", false],
       ["network.predictor.enable-prefetch", false],
+      ["browser.cache.cache_isolation", false],
     ],
   });
   clearAllImageCaches();
diff --git a/browser/components/originattributes/test/browser/browser_imageCacheIsolation.js b/browser/components/originattributes/test/browser/browser_imageCacheIsolation.js
index 89bb6f214a59..3c107ac465b1 100644
--- a/browser/components/originattributes/test/browser/browser_imageCacheIsolation.js
+++ b/browser/components/originattributes/test/browser/browser_imageCacheIsolation.js
@@ -19,6 +19,8 @@ server.start(-1);
 // Disable rcwn to make cache behavior deterministic.
 let rcwnEnabled = Services.prefs.getBoolPref("network.http.rcwn.enabled");
 Services.prefs.setBoolPref("network.http.rcwn.enabled", false);
+// Disable additional Http cache isolation.
+Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
 
 registerCleanupFunction(() => {
   Services.prefs.setBoolPref("network.http.rcwn.enabled", rcwnEnabled);
diff --git a/modules/libpref/init/StaticPrefList.yaml b/modules/libpref/init/StaticPrefList.yaml
index cacbf5924885..4b7d0c006784 100644
--- a/modules/libpref/init/StaticPrefList.yaml
+++ b/modules/libpref/init/StaticPrefList.yaml
@@ -687,7 +687,12 @@
 # Enable/Disable Origin based cache isolation
 - name: browser.cache.cache_isolation
   type: RelaxedAtomicBool
+
+#if defined(NIGHTLY_BUILD)
+  value: true
+#else
   value: false
+#endif
   mirror: always
 
 # -1 = determine dynamically, 0 = none, n = memory capacity in kilobytes.
diff --git a/netwerk/test/browser/browser_about_cache.js b/netwerk/test/browser/browser_about_cache.js
index 29bdea6fb822..a64f12e41585 100644
--- a/netwerk/test/browser/browser_about_cache.js
+++ b/netwerk/test/browser/browser_about_cache.js
@@ -4,6 +4,9 @@
  * Open a dummy page, then open about:cache and verify the opened page shows up in the cache.
  */
 add_task(async function() {
+  await SpecialPowers.pushPrefEnv({
+    set: [["browser.cache.cache_isolation", false]],
+  });
   const kRoot = getRootDirectory(gTestPath).replace(
     "chrome://mochitests/content/",
     "https://example.com/"
diff --git a/netwerk/test/unit/test_alt-data_closeWithStatus.js b/netwerk/test/unit/test_alt-data_closeWithStatus.js
index f8245e4f726f..2c14c6c5cc5c 100644
--- a/netwerk/test/unit/test_alt-data_closeWithStatus.js
+++ b/netwerk/test/unit/test_alt-data_closeWithStatus.js
@@ -11,6 +11,7 @@
  */
 
 const { HttpServer } = ChromeUtils.import("resource://testing-common/httpd.js");
+var { Services } = ChromeUtils.import("resource://gre/modules/Services.jsm");
 
 XPCOMUtils.defineLazyGetter(this, "URL", function() {
   return "http://localhost:" + httpServer.identity.primaryPort + "/content";
@@ -79,6 +80,10 @@ function check_has_alt_data_in_index(aHasAltData) {
 }
 
 function run_test() {
+  if (!inChildProcess()) {
+    Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+  }
+
   do_get_profile();
   httpServer = new HttpServer();
   httpServer.registerPathHandler("/content", contentHandler);
diff --git a/netwerk/test/unit/test_alt-data_simple.js b/netwerk/test/unit/test_alt-data_simple.js
index 0d2788203188..ea88f8e33fa5 100644
--- a/netwerk/test/unit/test_alt-data_simple.js
+++ b/netwerk/test/unit/test_alt-data_simple.js
@@ -10,6 +10,7 @@
  */
 
 const { HttpServer } = ChromeUtils.import("resource://testing-common/httpd.js");
+var { Services } = ChromeUtils.import("resource://gre/modules/Services.jsm");
 
 XPCOMUtils.defineLazyGetter(this, "URL", function() {
   return "http://localhost:" + httpServer.identity.primaryPort + "/content";
@@ -68,6 +69,9 @@ function check_has_alt_data_in_index(aHasAltData) {
 }
 
 function run_test() {
+  if (!inChildProcess()) {
+    Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+  }
   do_get_profile();
   httpServer = new HttpServer();
   httpServer.registerPathHandler("/content", contentHandler);
diff --git a/netwerk/test/unit/test_bug1064258.js b/netwerk/test/unit/test_bug1064258.js
index 34d11977f072..817338e53744 100644
--- a/netwerk/test/unit/test_bug1064258.js
+++ b/netwerk/test/unit/test_bug1064258.js
@@ -53,6 +53,8 @@ function contentHandler2(metadata, response) {
 }
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+
   httpServer = new HttpServer();
   httpServer.registerPathHandler("/content1", contentHandler1);
   httpServer.registerPathHandler("/content2", contentHandler2);
diff --git a/netwerk/test/unit/test_bug482601.js b/netwerk/test/unit/test_bug482601.js
index 8f5f9b6b782c..69f1f45737bf 100644
--- a/netwerk/test/unit/test_bug482601.js
+++ b/netwerk/test/unit/test_bug482601.js
@@ -37,6 +37,8 @@ var listener = {
 };
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+
   httpserv = new HttpServer();
   httpserv.registerPathHandler("/bug482601/nocache", bug482601_nocache);
   httpserv.registerPathHandler("/bug482601/partial", bug482601_partial);
diff --git a/netwerk/test/unit/test_bug482934.js b/netwerk/test/unit/test_bug482934.js
index e84584236ccc..7e36d86e52b9 100644
--- a/netwerk/test/unit/test_bug482934.js
+++ b/netwerk/test/unit/test_bug482934.js
@@ -9,7 +9,6 @@ var request_time;
 var response_time;
 
 var cache_storage;
-
 var httpserver = new HttpServer();
 httpserver.start(-1);
 
@@ -69,6 +68,8 @@ function check_cached_data(aCachedData, aCallback) {
 }
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+
   do_get_profile();
   evict_cache_entries();
 
diff --git a/netwerk/test/unit/test_bug618835.js b/netwerk/test/unit/test_bug618835.js
index ad80e75a18f2..c5077aaaef4a 100644
--- a/netwerk/test/unit/test_bug618835.js
+++ b/netwerk/test/unit/test_bug618835.js
@@ -80,6 +80,8 @@ FinalListener.prototype = {
 };
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
+
   httpserv = new HttpServer();
   httpserv.registerPathHandler("/cl", content_location);
   httpserv.registerPathHandler("/post", post_target);
diff --git a/netwerk/test/unit/test_bug812167.js b/netwerk/test/unit/test_bug812167.js
index 5006158c3a38..04b40ced11ea 100644
--- a/netwerk/test/unit/test_bug812167.js
+++ b/netwerk/test/unit/test_bug812167.js
@@ -127,6 +127,7 @@ function finish_test() {
 
 function run_test() {
   do_get_profile();
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
 
   httpserver = new HttpServer();
   httpserver.registerPathHandler(randomPath1, redirectHandler_NoStore);
diff --git a/netwerk/test/unit/test_cache-control_request.js b/netwerk/test/unit/test_cache-control_request.js
index a6180b50d62e..d0e3e6885b8f 100644
--- a/netwerk/test/unit/test_cache-control_request.js
+++ b/netwerk/test/unit/test_cache-control_request.js
@@ -79,6 +79,7 @@ function run_test() {
   do_test_pending();
 
   Services.prefs.setBoolPref("network.http.rcwn.enabled", false);
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
 
   httpserver.registerPathHandler(resource_age_100, resource_age_100_handler);
   httpserver.registerPathHandler(
diff --git a/netwerk/test/unit/test_http2.js b/netwerk/test/unit/test_http2.js
index 990a708bee2f..a612f26bb698 100644
--- a/netwerk/test/unit/test_http2.js
+++ b/netwerk/test/unit/test_http2.js
@@ -1407,6 +1407,7 @@ function run_test() {
   prefs.setBoolPref("network.http.spdy.enabled.http2", true);
   prefs.setBoolPref("network.http.altsvc.enabled", true);
   prefs.setBoolPref("network.http.altsvc.oe", true);
+  prefs.setBoolPref("browser.cache.cache_isolation", false);
   prefs.setCharPref(
     "network.dns.localDomains",
     "foo.example.com, bar.example.com"
diff --git a/netwerk/test/unit/test_inhibit_caching.js b/netwerk/test/unit/test_inhibit_caching.js
index 6b1e6531862a..47c9a696afec 100644
--- a/netwerk/test/unit/test_inhibit_caching.js
+++ b/netwerk/test/unit/test_inhibit_caching.js
@@ -19,6 +19,7 @@ var httpserver = null;
 
 function run_test() {
   // setup test
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
   httpserver = new HttpServer();
   httpserver.registerPathHandler("/test", contentHandler);
   httpserver.start(-1);
diff --git a/netwerk/test/unit/test_predictor.js b/netwerk/test/unit/test_predictor.js
index 9d21a6fd3267..309255e514ff 100644
--- a/netwerk/test/unit/test_predictor.js
+++ b/netwerk/test/unit/test_predictor.js
@@ -739,6 +739,7 @@ function run_test_real() {
   tests.forEach(f => add_test(f));
   do_get_profile();
 
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
   Services.prefs.setBoolPref("network.predictor.enabled", true);
   Services.prefs.setBoolPref("network.predictor.cleaned-up", true);
   Services.prefs.setBoolPref("network.predictor.doing-tests", true);
diff --git a/netwerk/test/unit/test_protocolproxyservice.js b/netwerk/test/unit/test_protocolproxyservice.js
index ab8e58380336..6dc1cd6931b7 100644
--- a/netwerk/test/unit/test_protocolproxyservice.js
+++ b/netwerk/test/unit/test_protocolproxyservice.js
@@ -25,6 +25,8 @@ var pps = Cc["@mozilla.org/network/protocol-proxy-service;1"].getService();
 var prefs = Cc["@mozilla.org/preferences-service;1"].getService(
   Ci.nsIPrefBranch
 );
+var { Services } = ChromeUtils.import("resource://gre/modules/Services.jsm");
+Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
 
 /**
  * Test nsIProtocolHandler that allows proxying, but doesn't allow HTTP
diff --git a/netwerk/test/unit/test_suspend_channel_on_examine_merged_response.js b/netwerk/test/unit/test_suspend_channel_on_examine_merged_response.js
index 7228b7b6850c..c4d902948df6 100644
--- a/netwerk/test/unit/test_suspend_channel_on_examine_merged_response.js
+++ b/netwerk/test/unit/test_suspend_channel_on_examine_merged_response.js
@@ -55,6 +55,7 @@ var listener = {
 };
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
   httpserv = new HttpServer();
   httpserv.registerPathHandler("/path/partial", path_partial);
   httpserv.registerPathHandler("/path/cached", path_cached);
diff --git a/netwerk/test/unit_ipc/test_alt-data_closeWithStatus_wrap.js b/netwerk/test/unit_ipc/test_alt-data_closeWithStatus_wrap.js
index d2beb0fa17c0..fdf48ecbc975 100644
--- a/netwerk/test/unit_ipc/test_alt-data_closeWithStatus_wrap.js
+++ b/netwerk/test/unit_ipc/test_alt-data_closeWithStatus_wrap.js
@@ -11,6 +11,7 @@ var cacheFlushObserver = {
 var currentThread = Services.tm.currentThread;
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
   do_get_profile();
   do_await_remote_message("flush").then(() => {
     Services.cache2
diff --git a/netwerk/test/unit_ipc/test_alt-data_simple_wrap.js b/netwerk/test/unit_ipc/test_alt-data_simple_wrap.js
index 06f51785139c..f2f0690db9de 100644
--- a/netwerk/test/unit_ipc/test_alt-data_simple_wrap.js
+++ b/netwerk/test/unit_ipc/test_alt-data_simple_wrap.js
@@ -9,6 +9,7 @@ var cacheFlushObserver = {
 };
 
 function run_test() {
+  Services.prefs.setBoolPref("browser.cache.cache_isolation", false);
   do_get_profile();
   do_await_remote_message("flush").then(() => {
     Services.cache2
diff --git a/testing/web-platform/meta/fetch/http-cache/invalidate.html.ini b/testing/web-platform/meta/fetch/http-cache/invalidate.html.ini
index d203e090672a..a74a80459c10 100644
--- a/testing/web-platform/meta/fetch/http-cache/invalidate.html.ini
+++ b/testing/web-platform/meta/fetch/http-cache/invalidate.html.ini
@@ -1,4 +1,5 @@
 [invalidate.html]
+  prefs: [browser.cache.cache_isolation:false]
   [HTTP cache does not invalidate after a failed response from an unsafe request]
     expected: FAIL
 
diff --git a/toolkit/components/antitracking/test/browser/browser_networkIsolation.js b/toolkit/components/antitracking/test/browser/browser_networkIsolation.js
index 4e24bcc5f0d6..c7efecabd9f8 100644
--- a/toolkit/components/antitracking/test/browser/browser_networkIsolation.js
+++ b/toolkit/components/antitracking/test/browser/browser_networkIsolation.js
@@ -37,6 +37,7 @@ add_task(async function() {
     set: [
       ["browser.cache.disk.enable", false],
       ["browser.cache.memory.enable", false],
+      ["browser.cache.cache_isolation", false],
       [
         "network.cookie.cookieBehavior",
         Ci.nsICookieService.BEHAVIOR_REJECT_TRACKER,