diff --git src/wp-admin/includes/update-core.php src/wp-admin/includes/update-core.php
index 6d9d243ddd2..9d0452dbcbc 100644
--- src/wp-admin/includes/update-core.php
+++ src/wp-admin/includes/update-core.php
@@ -946,6 +946,15 @@ function update_core( $from, $to ) {
 	}
 
 	$wp_filesystem->chmod( $versions_file, FS_CHMOD_FILE );
+
+	/*
+	 * `wp_opcache_invalidate()` only exists in WordPress 5.5 or later,
+	 * so don't run it when upgrading from older versions.
+	 */
+	if ( function_exists( 'wp_opcache_invalidate' ) ) {
+		wp_opcache_invalidate( $versions_file );
+	}
+
 	require WP_CONTENT_DIR . '/upgrade/version-current.php';
 	$wp_filesystem->delete( $versions_file );
 
@@ -1117,6 +1126,14 @@ function update_core( $from, $to ) {
 			$result = new WP_Error( 'copy_failed_for_version_file', __( 'The update cannot be installed because we will be unable to copy some files. This is usually due to inconsistent file permissions.' ), 'wp-includes/version.php' );
 		}
 		$wp_filesystem->chmod( $to . 'wp-includes/version.php', FS_CHMOD_FILE );
+
+		/*
+		 * `wp_opcache_invalidate()` only exists in WordPress 5.5 or later,
+		 * so don't run it when upgrading from older versions.
+		 */
+		if ( function_exists( 'wp_opcache_invalidate' ) ) {
+			wp_opcache_invalidate( $to . 'wp-includes/version.php' );
+		}
 	}
 
 	// Check to make sure everything copied correctly, ignoring the contents of wp-content.