diff --git src/wp-includes/class-wp-meta-query.php src/wp-includes/class-wp-meta-query.php
index 6db272c526..61beeb3f3c 100644
--- src/wp-includes/class-wp-meta-query.php
+++ src/wp-includes/class-wp-meta-query.php
@@ -99,6 +99,7 @@ class WP_Meta_Query {
 	 *
 	 * @since 3.2.0
 	 * @since 4.2.0 Introduced support for naming query clauses by associative array keys.
+	 * @since 5.0.0 Introduced $compare_key clause parameter, which enables LIKE key matches.
 	 *
 	 * @param array $meta_query {
 	 *     Array of meta query clauses. When first-order clauses or sub-clauses use strings as
@@ -109,17 +110,18 @@ class WP_Meta_Query {
 	 *     @type array {
 	 *         Optional. An array of first-order clause parameters, or another fully-formed meta query.
 	 *
-	 *         @type string $key     Meta key to filter by.
-	 *         @type string $value   Meta value to filter by.
-	 *         @type string $compare MySQL operator used for comparing the $value. Accepts '=',
-	 *                               '!=', '>', '>=', '<', '<=', 'LIKE', 'NOT LIKE',
-	 *                               'IN', 'NOT IN', 'BETWEEN', 'NOT BETWEEN', 'REGEXP',
-	 *                               'NOT REGEXP', 'RLIKE', 'EXISTS' or 'NOT EXISTS'.
-	 *                               Default is 'IN' when `$value` is an array, '=' otherwise.
-	 *         @type string $type    MySQL data type that the meta_value column will be CAST to for
-	 *                               comparisons. Accepts 'NUMERIC', 'BINARY', 'CHAR', 'DATE',
-	 *                               'DATETIME', 'DECIMAL', 'SIGNED', 'TIME', or 'UNSIGNED'.
-	 *                               Default is 'CHAR'.
+	 *         @type string $key         Meta key to filter by.
+	 *         @type string $compare_key MySQL operator used for comparing the $key. Accepts '=' and 'LIKE'.
+	 *         @type string $value       Meta value to filter by.
+	 *         @type string $compare     MySQL operator used for comparing the $value. Accepts '=',
+	 *                                   '!=', '>', '>=', '<', '<=', 'LIKE', 'NOT LIKE',
+	 *                                   'IN', 'NOT IN', 'BETWEEN', 'NOT BETWEEN', 'REGEXP',
+	 *                                   'NOT REGEXP', 'RLIKE', 'EXISTS' or 'NOT EXISTS'.
+	 *                                   Default is 'IN' when `$value` is an array, '=' otherwise.
+	 *         @type string $type        MySQL data type that the meta_value column will be CAST to for
+	 *                                   comparisons. Accepts 'NUMERIC', 'BINARY', 'CHAR', 'DATE',
+	 *                                   'DATETIME', 'DECIMAL', 'SIGNED', 'TIME', or 'UNSIGNED'.
+	 *                                   Default is 'CHAR'.
 	 *     }
 	 * }
 	 */
@@ -236,7 +238,7 @@ class WP_Meta_Query {
 		 * the rest of the meta_query).
 		 */
 		$primary_meta_query = array();
-		foreach ( array( 'key', 'compare', 'type' ) as $key ) {
+		foreach ( array( 'key', 'compare', 'type', 'compare_key' ) as $key ) {
 			if ( ! empty( $qv[ "meta_$key" ] ) ) {
 				$primary_meta_query[ $key ] = $qv[ "meta_$key" ];
 			}
@@ -518,7 +520,14 @@ class WP_Meta_Query {
 			$clause['compare'] = '=';
 		}
 
+		if ( isset( $clause['compare_key'] ) && 'LIKE' === strtoupper( $clause['compare_key'] ) ) {
+			$clause['compare_key'] = strtoupper( $clause['compare_key'] );
+		} else {
+			$clause['compare_key'] = '=';
+		}
+
 		$meta_compare = $clause['compare'];
+		$meta_compare_key = $clause['compare_key'];
 
 		// First build the JOIN clause, if one is required.
 		$join = '';
@@ -533,7 +542,12 @@ class WP_Meta_Query {
 			if ( 'NOT EXISTS' === $meta_compare ) {
 				$join .= " LEFT JOIN $this->meta_table";
 				$join .= $i ? " AS $alias" : '';
-				$join .= $wpdb->prepare( " ON ($this->primary_table.$this->primary_id_column = $alias.$this->meta_id_column AND $alias.meta_key = %s )", $clause['key'] );
+
+				if ( 'LIKE' === $meta_compare_key ) {
+					$join .= $wpdb->prepare( " ON ($this->primary_table.$this->primary_id_column = $alias.$this->meta_id_column AND $alias.meta_key LIKE %s )", '%' . $wpdb->esc_like( $clause['key'] ) . '%' );
+				} else  {
+					$join .= $wpdb->prepare( " ON ($this->primary_table.$this->primary_id_column = $alias.$this->meta_id_column AND $alias.meta_key = %s )", $clause['key'] );
+				}
 
 				// All other JOIN clauses.
 			} else {
@@ -577,7 +591,11 @@ class WP_Meta_Query {
 			if ( 'NOT EXISTS' === $meta_compare ) {
 				$sql_chunks['where'][] = $alias . '.' . $this->meta_id_column . ' IS NULL';
 			} else {
-				$sql_chunks['where'][] = $wpdb->prepare( "$alias.meta_key = %s", trim( $clause['key'] ) );
+				if ( 'LIKE' === $meta_compare_key ) {
+					$sql_chunks['where'][] = $wpdb->prepare( "$alias.meta_key LIKE %s", '%' . $wpdb->esc_like( trim( $clause['key'] ) ) . '%' );
+				} else  {
+					$sql_chunks['where'][] = $wpdb->prepare( "$alias.meta_key = %s", trim( $clause['key'] ) );
+				}
 			}
 		}
 
diff --git src/wp-includes/class-wp-query.php src/wp-includes/class-wp-query.php
index 930e33d883..3d92c340e2 100644
--- src/wp-includes/class-wp-query.php
+++ src/wp-includes/class-wp-query.php
@@ -640,6 +640,7 @@ class WP_Query {
 	 *     @type int          $m                       Combination YearMonth. Accepts any four-digit year and month
 	 *                                                 numbers 1-12. Default empty.
 	 *     @type string       $meta_compare            Comparison operator to test the 'meta_value'.
+	 *     @type string       $meta_compare_key        Comparison operator to test the 'meta_key'.
 	 *     @type string       $meta_key                Custom field key.
 	 *     @type array        $meta_query              An associative array of WP_Meta_Query arguments. See WP_Meta_Query.
 	 *     @type string       $meta_value              Custom field value.
diff --git tests/phpunit/tests/query/metaQuery.php tests/phpunit/tests/query/metaQuery.php
index bed26a4213..8a8e93b044 100644
--- tests/phpunit/tests/query/metaQuery.php
+++ tests/phpunit/tests/query/metaQuery.php
@@ -1848,4 +1848,50 @@ class Tests_Query_MetaQuery extends WP_UnitTestCase {
 
 		$this->assertEqualSets( array( 'foo_key', 'foo_key-1', 'foo_key-2' ), array_keys( $q->meta_query->get_clauses() ) );
 	}
+
+	/**
+	 * @ticket 42409
+	 */
+	public function test_compare_key_like() {
+		$posts = self::factory()->post->create_many( 3 );
+
+		add_post_meta( $posts[0], 'aaa_foo_aaa', 'abc' );
+		add_post_meta( $posts[1], 'aaa_bar_aaa', 'abc' );
+		add_post_meta( $posts[2], 'aaa_foo_bbb', 'abc' );
+
+		$q = new WP_Query(
+			array(
+				'meta_query' => array(
+					array(
+						'compare_key' => 'LIKE',
+						'key'         => 'aa_foo',
+					),
+				),
+				'fields' => 'ids',
+			)
+		);
+
+		$this->assertEqualSets( array( $posts[0], $posts[2] ), $q->posts );
+	}
+
+	/**
+	 * @ticket 42409
+	 */
+	public function test_meta_compare_key_like() {
+		$posts = self::factory()->post->create_many( 3 );
+
+		add_post_meta( $posts[0], 'aaa_foo_aaa', 'abc' );
+		add_post_meta( $posts[1], 'aaa_bar_aaa', 'abc' );
+		add_post_meta( $posts[2], 'aaa_foo_bbb', 'abc' );
+
+		$q = new WP_Query(
+			array(
+				'meta_compare_key' => 'LIKE',
+				'meta_key'         => 'aa_foo',
+				'fields'           => 'ids',
+			)
+		);
+
+		$this->assertEqualSets( array( $posts[0], $posts[2] ), $q->posts );
+	}
 }