Rock started his career as a cast member on Saturday Night Live from 1990 to 1993 alongside Adam Sandler, David Spade, and Chris Farley.

During this time Rock gained stardom as a standup comedian releasing several comedy albums including Born Suspect (1991), Roll with the New (1997), and Bigger & Blacker (1999).

In 2003 he made his directorial debut with the political satire Head of State (2003), followed by his films as a director I Think I Love My Wife (2007) and Top Five (2014).

Rock has also made appearances in a variety of television shows including Louie (2011–2012), Comedians in Cars Getting Coffee (2013), Broad City (2015), Empire (2015), and Fargo (2020).

He also is known for his vocal performances as titular protagonist of Osmosis Jones (2001), Marty the Zebra in DreamWorks Animation's Madagascar film franchise (2005–2012) and as Mooseblood in Jerry Seinfeld's Bee Movie (2007).