Derek Richardson began his career in regional theater and off-Broadway productions before he began to land roles on television. His first role was on an episode of Law & Order in 2000, and he later obtained a recurring role as Adam Davis on the WB hit Felicity in 2002. He has also appeared in Strangers with Candy on Comedy Central.
Richardson made his feature film debut playing the starring role of Harry Dunne in the prequel Dumb and Dumberer: When Harry Met Lloyd (2003), taking on the role that Jeff Daniels originated in the highly popular 1994 film, Dumb and Dumber. For his work, he shared a 2003 Teen Choice Award nomination for Choice Movie Chemistry and a 2004 Razzie Award nomination for Worst Screen Couple.