diff --git a/src/controllers/SystemSettingsController.php b/src/controllers/SystemSettingsController.php
index b8eb9f72f5b..f705586c1cf 100644
--- a/src/controllers/SystemSettingsController.php
+++ b/src/controllers/SystemSettingsController.php
@@ -334,6 +334,7 @@ private function _createMailSettingsFromPost(): MailSettings
         $settings->template = $this->request->getBodyParam('template');
         $settings->transportType = $this->request->getBodyParam('transportType');
         $settings->transportSettings = Component::cleanseConfig($this->request->getBodyParam(sprintf('transportTypes.%s', Html::id($settings->transportType))) ?? []);
+        $settings->setSiteOverrides($this->request->getBodyParam('siteOverrides') ?? []);
 
         return $settings;
     }
diff --git a/src/helpers/App.php b/src/helpers/App.php
index 0ca7b5033e4..38c8dd45ea3 100644
--- a/src/helpers/App.php
+++ b/src/helpers/App.php
@@ -1045,6 +1045,7 @@ public static function mailerConfig(?MailSettings $settings = null): array
             ],
             'replyTo' => App::parseEnv($settings->replyToEmail),
             'template' => App::parseEnv($settings->template),
+            'siteOverrides' => $settings->getSiteOverrides(),
             'transport' => $adapter->defineTransport(),
         ];
     }
diff --git a/src/mail/Mailer.php b/src/mail/Mailer.php
index d4421ac0b96..366066d2e1a 100644
--- a/src/mail/Mailer.php
+++ b/src/mail/Mailer.php
@@ -12,6 +12,7 @@
 use craft\enums\CmsEdition;
 use craft\helpers\App;
 use craft\helpers\Template;
+use craft\models\Site;
 use craft\web\View;
 use Throwable;
 use yii\base\InvalidConfigException;
@@ -49,6 +50,12 @@ class Mailer extends \yii\symfonymailer\Mailer
      */
     public User|string|array|null $replyTo = null;
 
+    /**
+     * @var array Site overrides
+     * @since 5.6.0
+     */
+    public array $siteOverrides = [];
+
     /**
      * Composes a new email based on a given key.
      *
@@ -93,12 +100,14 @@ public function send($message): bool
         ]));
 
         $generalConfig = Craft::$app->getConfig()->getGeneral();
-
-        if ($message instanceof Message && $message->key !== null) {
-            $sitesService = Craft::$app->getSites();
-            $currentSite = $messageSite = null;
-
-            if (isset($message->siteId)) {
+        $sitesService = Craft::$app->getSites();
+        $currentSite = $messageSite = null;
+        $language = Craft::$app->language;
+        $generateTransformsBeforePageLoad = $generalConfig->generateTransformsBeforePageLoad;
+        $originalSettings = [];
+
+        try {
+            if ($message instanceof Message && isset($message->siteId)) {
                 $messageSite = $sitesService->getSiteById($message->siteId);
                 if ($messageSite) {
                     $currentSite = $sitesService->getCurrentSite();
@@ -106,27 +115,44 @@ public function send($message): bool
                 }
             }
 
-            if ($message->language === null) {
-                // If a site was specified, go with its language
-                if ($messageSite) {
-                    $message->language = $messageSite->language;
-                } else {
-                    // Default to the current language
-                    $message->language = Craft::$app->getRequest()->getIsSiteRequest()
-                        ? Craft::$app->language
-                        : Craft::$app->getSites()->getPrimarySite()->language;
-                }
+            $overrides = $this->siteOverrides[$sitesService->getCurrentSite()->uid] ?? [];
+            if (isset($overrides['fromEmail']) || isset($overrides['fromName'])) {
+                $originalSettings['from'] = $this->from;
+                $fromEmail = $overrides['fromEmail'] ?? array_key_first($this->from);
+                $fromName = $overrides['fromName'] ?? reset($this->from);
+                /** @phpstan-ignore-next-line */
+                $this->from = [
+                    App::parseEnv($fromEmail) => App::parseEnv($fromName),
+                ];
+            }
+            if (isset($overrides['replyToEmail'])) {
+                $originalSettings['replyTo'] = $this->replyTo;
+                $this->replyTo = App::parseEnv($overrides['replyToEmail']);
             }
+            if (isset($overrides['template'])) {
+                $originalSettings['template'] = $this->template;
+                $this->template = App::parseEnv($overrides['template']);
+            }
+
+            if ($message instanceof Message && $message->key !== null) {
+                if ($message->language === null) {
+                    // If a site was specified, go with its language
+                    if ($messageSite) {
+                        $message->language = $messageSite->language;
+                    } else {
+                        // Default to the current language
+                        $message->language = Craft::$app->getRequest()->getIsSiteRequest()
+                            ? Craft::$app->language
+                            : Craft::$app->getSites()->getPrimarySite()->language;
+                    }
+                }
 
-            // Use the message language
-            $language = Craft::$app->language;
-            Craft::$app->language = $message->language;
+                // Use the message language
+                Craft::$app->language = $message->language;
 
-            // Temporarily disable lazy transform generation
-            $generateTransformsBeforePageLoad = $generalConfig->generateTransformsBeforePageLoad;
-            $generalConfig->generateTransformsBeforePageLoad = true;
+                // Temporarily disable lazy transform generation
+                $generalConfig->generateTransformsBeforePageLoad = true;
 
-            try {
                 $systemMessage = Craft::$app->getSystemMessages()->getMessage($message->key, $message->language);
 
                 $settings = App::mailSettings();
@@ -169,34 +195,36 @@ public function send($message): bool
                     Craft::warning('Error rendering email template: ' . $e->getMessage(), __METHOD__);
                     Craft::$app->getErrorHandler()->logException($e);
                 }
-            } finally {
-                // Set things back to normal
-                Craft::$app->language = $language;
-                $generalConfig->generateTransformsBeforePageLoad = $generateTransformsBeforePageLoad;
+            }
 
-                if ($currentSite) {
-                    $sitesService->setCurrentSite($currentSite);
-                }
+            // Set the default sender if there isn't one already
+            if (!$message->getFrom()) {
+                $message->setFrom($this->from);
             }
-        }
 
-        // Set the default sender if there isn't one already
-        if (!$message->getFrom()) {
-            $message->setFrom($this->from);
-        }
+            if ($this->replyTo && !$message->getReplyTo()) {
+                $message->setReplyTo($this->replyTo);
+            }
 
-        if ($this->replyTo && !$message->getReplyTo()) {
-            $message->setReplyTo($this->replyTo);
-        }
+            // Apply the testToEmailAddress config setting
+            $testToEmailAddress = $generalConfig->getTestToEmailAddress();
+            if (!empty($testToEmailAddress)) {
+                $message->setTo($testToEmailAddress);
+                $message->setCc([]);
+                $message->setBcc([]);
+            }
 
-        // Apply the testToEmailAddress config setting
-        $testToEmailAddress = $generalConfig->getTestToEmailAddress();
-        if (!empty($testToEmailAddress)) {
-            $message->setTo($testToEmailAddress);
-            $message->setCc([]);
-            $message->setBcc([]);
-        }
+            return parent::send($message);
+        } finally {
+            // Set things back to normal
+            Craft::$app->language = $language;
+            $generalConfig->generateTransformsBeforePageLoad = $generateTransformsBeforePageLoad;
 
-        return parent::send($message);
+            if ($currentSite) {
+                $sitesService->setCurrentSite($currentSite);
+            }
+
+            Craft::configure($this, $originalSettings);
+        }
     }
 }
diff --git a/src/models/MailSettings.php b/src/models/MailSettings.php
index 1c22e6638d2..c47fb4acb34 100644
--- a/src/models/MailSettings.php
+++ b/src/models/MailSettings.php
@@ -13,6 +13,8 @@
 use craft\mail\transportadapters\Sendmail;
 use craft\mail\transportadapters\TransportAdapterInterface;
 use craft\validators\TemplateValidator;
+use Illuminate\Support\Collection;
+use yii\validators\EmailValidator;
 
 /**
  * MailSettings Model class.
@@ -43,6 +45,12 @@ class MailSettings extends Model
      */
     public ?string $template = null;
 
+    /**
+     * @var array Site-specific overrides
+     * @since 5.6.0
+     */
+    private array $siteOverrides = [];
+
     /**
      * @var class-string<TransportAdapterInterface>|null The transport type that should be used
      */
@@ -71,6 +79,27 @@ protected function defineBehaviors(): array
         ];
     }
 
+    /**
+     * @inheritdoc
+     */
+    public function attributes()
+    {
+        return [
+            ...parent::attributes(),
+            'siteOverrides',
+        ];
+    }
+
+    /**
+     * @inheritdoc
+     */
+    public function fields(): array
+    {
+        $fields = parent::fields();
+        $fields['siteOverrides'] = fn() => $this->siteOverrides;
+        return $fields;
+    }
+
     /**
      * @inheritdoc
      */
@@ -82,6 +111,7 @@ public function attributeLabels(): array
             'fromName' => Craft::t('app', 'Sender Name'),
             'template' => Craft::t('app', 'HTML Email Template'),
             'transportType' => Craft::t('app', 'Transport Type'),
+            'siteOverrides' => Craft::t('app', 'Site Overrides'),
         ];
     }
 
@@ -95,6 +125,53 @@ protected function defineRules(): array
         $rules[] = [['fromEmail', 'replyToEmail'], 'email'];
         $rules[] = [['template'], TemplateValidator::class];
 
+        $rules[] = [['siteOverrides'], function() {
+            $sitesService = Craft::$app->getSites();
+            foreach ($this->siteOverrides as $siteUid => $overrides) {
+                foreach (['fromEmail', 'replyToEmail'] as $key) {
+                    if (isset($overrides[$key])) {
+                        $validator = new EmailValidator([
+                            'message' => Craft::t('yii', '{attribute} is not a valid email address.', [
+                                'attribute' => sprintf(
+                                    '%s - %s',
+                                    $sitesService->getSiteByUid($siteUid)->getUiLabel(),
+                                    $this->attributeLabels()[$key],
+                                ),
+                            ]),
+                        ]);
+                        if (!$validator->validate($overrides[$key], $error)) {
+                            $this->addError('siteOverrides', $error);
+                        }
+                    }
+                }
+            }
+        }];
+
         return $rules;
     }
+
+    /**
+     * Returns the site overrides.
+     *
+     * @return array
+     * @since 5.6.0
+     */
+    public function getSiteOverrides(): array
+    {
+        return Collection::make(Craft::$app->getSites()->getAllSites())
+            ->keyBy(fn(Site $site) => $site->uid)
+            ->map(fn(Site $site) => $this->siteOverrides[$site->uid] ?? [])
+            ->all();
+    }
+
+    /**
+     * Sets the site overrides.
+     *
+     * @param array $siteOverrides
+     * @since 5.6.0
+     */
+    public function setSiteOverrides(array $siteOverrides): void
+    {
+        $this->siteOverrides = array_filter(array_map(fn(array $overrides) => array_filter($overrides), $siteOverrides));
+    }
 }
diff --git a/src/templates/settings/email/_index.twig b/src/templates/settings/email/_index.twig
index f5f9781c18c..7e5e1e3ffbc 100644
--- a/src/templates/settings/email/_index.twig
+++ b/src/templates/settings/email/_index.twig
@@ -98,6 +98,52 @@
         }) }}
     {% endif %}
 
+    {% if craft.app.isMultiSite %}
+        {{ forms.editableTableField({
+            label: 'Site Overrides'|t('app'),
+            instructions: 'Blank values will default to the settings above.'|t('app'),
+            id: 'site-overrides',
+            name: 'siteOverrides',
+            cols: {
+                heading: {
+                    type: 'heading',
+                    heading: 'Site'|t('app'),
+                    suggestEnvVars: true,
+                    thin: true,
+                },
+                fromEmail: {
+                    type: 'autosuggest',
+                    heading: 'System Email Address'|t('app'),
+                    suggestEnvVars: true,
+                },
+                replyToEmail: {
+                    type: 'autosuggest',
+                    heading: 'Reply-To Address'|t('app'),
+                    suggestEnvVars: true,
+                },
+                fromName: {
+                    type: 'autosuggest',
+                    heading: 'Sender Name'|t('app'),
+                    suggestEnvVars: true,
+                },
+                template: CraftEdition >= CraftPro ? {
+                    type: 'template',
+                    heading: 'HTML Email Template'|t('app'),
+                    suggestEnvVars: true,
+                    code: true,
+                }
+            }|filter,
+            rows: settings.siteOverrides|map((overrides, siteUid) => overrides|merge({
+                heading: craft.app.sites.getSiteByUid(siteUid).getUiLabel(),
+            })),
+            fullWidth: true,
+            allowAdd: false,
+            allowDelete: false,
+            allowReorder: false,
+            errors: (freshSettings ? null : settings.getErrors('siteOverrides')|unique),
+        }) }}
+    {% endif %}
+
     <hr>
 
     {{ forms.selectField({
diff --git a/src/translations/en/app.php b/src/translations/en/app.php
index d867da67eda..19946414d60 100644
--- a/src/translations/en/app.php
+++ b/src/translations/en/app.php
@@ -209,6 +209,7 @@
     'Base URL' => 'Base URL',
     'Before other {type}' => 'Before other {type}',
     'Before…' => 'Before…',
+    'Blank values will default to the settings above.' => 'Blank values will default to the settings above.',
     'Blue' => 'Blue',
     'Body' => 'Body',
     'Bottom-Center' => 'Bottom-Center',
@@ -1499,6 +1500,7 @@
     'Singles' => 'Singles',
     'Site Group' => 'Site Group',
     'Site Icon' => 'Site Icon',
+    'Site Overrides' => 'Site Overrides',
     'Site Settings' => 'Site Settings',
     'Site saved.' => 'Site saved.',
     'Site' => 'Site',