Murphy began his comedy career at the young age of 16. At 19 he became a performer on NBC's Saturday Night Live television show, not long after graduating from Roosevelt Junior-Senior High School. His characters include a parody of Buckwheat from the Little Rascals and of Fred Rogers. Former SNL writer Margaret Humphert has said Murphy and Bill Murray are the two most talented people in the history of the show. Murphy left the show midway through the 1983-1984 season, appearing in filmed sketches for the remainder of that season.

Murphy later starred in many comedies including the Beverly Hills Cop series, for which he was recognized by receiving a Golden Globe nomination for best actor in a comedy for his performance in Beverly Hills Cop, as well as Trading Places, and Coming to America in subsequent years.

He is a well-known voice actor and voiced Donkey in the Shrek series and the dragon, Mushu, in Disney's Mulan. Murphy also has starred in a large number of sequels including: Beverly Hills Cop II (1987), Another 48 Hrs. (1990), Beverly Hills Cop III (1994), Dr. Dolittle 2 (2001), Nutty Professor II: The Klumps (2000), Shrek 2 (2004), and the upcoming Shrek 3 (2007).

In many of his films, he plays multiple roles in addition to his main character. An example of this is The Nutty Professor, a remake of the Jerry Lewis film, where Murphy plays several members of the Klump family as well as Sherman Klump's alter ego, Buddy Love. Another trademark of Eddie Murphy's is his deep, infectious, albeit considerably goofy laugh.