From 1995 until 1999, Marlon Wayans co-starred in the WB sitcom The Wayans Brothers with his brother Shawn. Though primarily a comedic actor, he garnered considerable critical acclaim for his dramatic turn in Requiem for a Dream.

He has also produced the Scary Movie trilogy and White Chicks. He was sharply criticized for his performance in the 2000 movie Dungeons & Dragons as "Snails," the incompetent Rogue.