Mitchell made his first television appearance on BET’s Comic View in 1999 where he instantly became a favorite among the show’s loyal followers. Shortly after Comic View, Mitchell moved to both Los Angeles and New York City where he had several appearances on The Late Late Show with Craig Kilborn and two on Late Night with Conan O'Brien. In 2003, Mitchell became a featured player on Saturday Night Live. After two seasons, in 2005 he was promoted to full cast member. His screen time was drastically reduced after this promotion. On September 20, 2006, Saturday Night Live announced that the show was dropping Mitchell, Chris Parnell and Horatio Sanz from the show due to budget cuts. After his stint on SNL, he has continued to perform stand-up comedy and appeared in the films Who's Your Caddy?The Comebacks and Mad Money. From 2008 to 2009, Mitchell made several appearances on The Today Show as a guest correspondent and on Tyra and Chelsea Lately as a guest panelist. In 2010, he appeared in the Comedy Central sketch series Nick Swardson's Pretend Time. With the help of Quincy Jones’s son, QD3, Mitchell released his stand-up comedy available on DVD entitled Snap Famous. He is also a writer and offers relationship advice in Essence magazine. His 2007 book, Your Girlfriends Only Know So Much, gives dating advice to African-American women. In 2012, he participated in Fox's dating game showThe Choice. Mitchell also recurred as Darryl Parks, Chyna's father on the Disney Channel sitcom A.N.T. Farm. In January 2015, Mitchell appeared at Ron White’s Comedy Salute to the Troops. In 2016 Mitchell recurred as Harvey in the Showtime series Roadies. Mitchell also had a role in the film Barely Lethal. On December 4, 2019, Mitchell was cast as a series regular, playing Irwin on the Fox comedy Outmatched. The character is the best friend of main character Mike.
On September 13, 2008, he married Jessica Santos in Atlanta. On May 20, 2011, Mitchell and Santos divorced. He married again, in September 2013, to Adris DeBarge, daughter of singer El DeBarge.. Their eldest daughter was born in March 2015. Elle Kate is their youngest daughter.