diff --git c/src/wp-includes/functions.php w/src/wp-includes/functions.php
index 8ae58299d6..0dec6df4f5 100644
--- c/src/wp-includes/functions.php
+++ w/src/wp-includes/functions.php
@@ -5553,8 +5553,11 @@ function _device_can_upload() {
  * @return bool True if the path is a stream URL.
  */
 function wp_is_stream( $path ) {
-	$wrappers    = stream_get_wrappers();
-	$wrappers    = array_map( 'preg_quote', $wrappers );
+	$wrappers = stream_get_wrappers();
+	foreach ( $wrappers as &$wrapper ) {
+		$wrapper = preg_quote( $wrapper, '!' );
+	}
+
 	$wrappers_re = '(' . join( '|', $wrappers ) . ')';
 
 	return preg_match( "!^$wrappers_re://!", $path ) === 1;
diff --git c/tests/phpunit/tests/functions.php w/tests/phpunit/tests/functions.php
index d9e3d5fbb8..82d689984b 100644
--- c/tests/phpunit/tests/functions.php
+++ w/tests/phpunit/tests/functions.php
@@ -1451,4 +1451,38 @@ class Tests_Functions extends WP_UnitTestCase {
 
 		);
 	}
+
+	/**
+	 * Test wp_is_stream validation.
+	 *
+	 * @ticket 44533
+	 * @dataProvider data_test_wp_is_stream
+	 *
+	 * @param $path
+	 * @param $expected
+	 */
+	public function test_wp_is_stream( $path, $expected ) {
+		$this->assertSame( $expected, wp_is_stream( $path ) );
+	}
+
+	/**
+	 * Data provider for stream validation.
+	 *
+	 * @return array
+	 */
+	public function data_test_wp_is_stream() {
+		return array(
+			// Legitimate stream examples.
+			array( 'https://example.com', true ),
+			array( 'ftp://example.com', true ),
+			array( 'file:///path/to/some/file', true ),
+			array( 'php://some/php/file.php', true ),
+
+			// Non-stream examples.
+			array( 'fakestream://foo/bar/baz', false ),
+			array( '../../some/relative/path', false ),
+			array( 'some/other/relative/path', false ),
+			array( '/leading/relative/path', false ),
+		);
+	}
 }