diff --git a/src/wp-includes/canonical.php b/src/wp-includes/canonical.php
index 6faeab2c27de3..b4ca1092f22cc 100644
--- a/src/wp-includes/canonical.php
+++ b/src/wp-includes/canonical.php
@@ -1007,8 +1007,22 @@ function redirect_guess_404_permalink() {
 			$where .= $wpdb->prepare( ' AND DAYOFMONTH(post_date) = %d', get_query_var( 'day' ) );
 		}
 
-		// phpcs:ignore WordPress.DB.PreparedSQL.InterpolatedNotPrepared
-		$post_id = $wpdb->get_var( "SELECT ID FROM $wpdb->posts WHERE $where AND post_status IN ('" . implode( "', '", esc_sql( $publicly_viewable_statuses ) ) . "')" );
+		$query = "SELECT ID FROM $wpdb->posts WHERE $where AND post_status IN ('" . implode( "', '", esc_sql( $publicly_viewable_statuses ) ) . "')";
+
+		$key          = md5( $query );
+		$last_changed = wp_cache_get_last_changed( 'posts' );
+		$cache_key    = "redirect_guess_404_permalink:$key";
+		$cache        = wp_cache_get_salted( $cache_key, 'post-queries', $last_changed );
+
+		if ( false !== $cache ) {
+			$post_id = $cache;
+		} else {
+			// phpcs:ignore WordPress.DB.PreparedSQL.NotPrepared
+			$post_id = (int) $wpdb->get_var( $query );
+
+			// We cache misses as well as hits.
+			wp_cache_set_salted( $cache_key, $post_id, 'post-queries', $last_changed );
+		}
 
 		if ( ! $post_id ) {
 			return false;
diff --git a/tests/phpunit/tests/canonical.php b/tests/phpunit/tests/canonical.php
index 886b09312910e..d8bc76c6d87c6 100644
--- a/tests/phpunit/tests/canonical.php
+++ b/tests/phpunit/tests/canonical.php
@@ -416,6 +416,121 @@ public function data_redirect_guess_404_permalink_post_types() {
 		);
 	}
 
+	/**
+	 * @ticket 64250
+	 *
+	 * @covers ::redirect_guess_404_permalink
+	 */
+	public function test_redirect_guess_404_permalink_cache() {
+		$post = self::factory()->post->create(
+			array(
+				'post_title' => 'redirect-guess-404-permalink-cache',
+			)
+		);
+
+		$this->go_to( 'redirect-guess-404-permalink-cach' );
+
+		$first_run = redirect_guess_404_permalink();
+		$this->assertSame( get_permalink( $post ), $first_run, 'Did not guess the correct permalink on first run.' );
+
+		$num_queries = get_num_queries();
+		$second_run  = redirect_guess_404_permalink();
+		$this->assertSame( $first_run, $second_run, 'Result changed between cached and uncached run.' );
+		$this->assertSame( $num_queries, get_num_queries(), 'A cached lookup performed an additional database query.' );
+	}
+
+	/**
+	 * @ticket 64250
+	 *
+	 * @covers ::redirect_guess_404_permalink
+	 */
+	public function test_redirect_guess_404_permalink_cache_misses_are_cached() {
+		$this->go_to( 'redirect-guess-404-permalink-no-such-post' );
+
+		$this->assertFalse( redirect_guess_404_permalink(), 'Expected no match for a nonexistent slug.' );
+
+		$num_queries = get_num_queries();
+		$this->assertFalse( redirect_guess_404_permalink() );
+		$this->assertSame( $num_queries, get_num_queries(), 'A cached "not found" result performed an additional database query.' );
+	}
+
+	/**
+	 * @ticket 64250
+	 *
+	 * @covers ::redirect_guess_404_permalink
+	 */
+	public function test_redirect_guess_404_permalink_cache_invalidated_on_new_matching_post() {
+		$this->go_to( 'redirect-guess-404-permalink-new-post' );
+
+		// Prime a "not found" cache entry.
+		$this->assertFalse( redirect_guess_404_permalink() );
+
+		$post = self::factory()->post->create(
+			array(
+				'post_title' => 'redirect-guess-404-permalink-new-post',
+			)
+		);
+
+		$num_queries = get_num_queries();
+		$this->assertSame( get_permalink( $post ), redirect_guess_404_permalink(), 'Newly created matching post was not found after cache invalidation.' );
+		$this->assertSame( 1, get_num_queries() - $num_queries, 'Expected exactly one new query after the posts cache was invalidated.' );
+	}
+
+	/**
+	 * @ticket 64250
+	 *
+	 * @covers ::redirect_guess_404_permalink
+	 */
+	public function test_redirect_guess_404_permalink_cache_invalidated_on_post_delete() {
+		$post = self::factory()->post->create(
+			array(
+				'post_title' => 'redirect-guess-404-permalink-delete-me',
+			)
+		);
+
+		$this->go_to( 'redirect-guess-404-permalink-delete-m' );
+
+		$this->assertSame( get_permalink( $post ), redirect_guess_404_permalink() );
+
+		wp_delete_post( $post, true );
+
+		$num_queries = get_num_queries();
+		$this->assertFalse( redirect_guess_404_permalink(), 'Deleted post should no longer be guessed after cache invalidation.' );
+		$this->assertSame( 1, get_num_queries() - $num_queries, 'Expected exactly one new query after the posts cache was invalidated by deletion.' );
+	}
+
+	/**
+	 * @ticket 64250
+	 *
+	 * @covers ::redirect_guess_404_permalink
+	 */
+	public function test_redirect_guess_404_permalink_cache_keys_do_not_collide() {
+		$post_post = self::factory()->post->create(
+			array(
+				'post_title' => 'redirect-guess-collision',
+				'post_type'  => 'post',
+			)
+		);
+		$page_post = self::factory()->post->create(
+			array(
+				'post_title' => 'redirect-guess-collision',
+				'post_type'  => 'page',
+			)
+		);
+
+		$this->go_to( '/?name=redirect-guess-collisio&post_type=post' );
+		$this->assertSame( get_permalink( $post_post ), redirect_guess_404_permalink() );
+
+		$this->go_to( '/?name=redirect-guess-collisio&post_type=page' );
+		$this->assertSame( get_permalink( $page_post ), redirect_guess_404_permalink(), 'Different post_type query var produced a colliding cached result.' );
+
+		// Re-run both to confirm both are independently cached and correct.
+		$this->go_to( '/?name=redirect-guess-collisio&post_type=post' );
+		$num_queries = get_num_queries();
+		$this->assertSame( get_permalink( $post_post ), redirect_guess_404_permalink() );
+		$this->assertSame( $num_queries, get_num_queries() );
+	}
+
 	/**
 	 * @ticket 43745
 	 */