Paula Poundstone started doing stand-up comedy on open-mike nights in Boston in 1979 and then relocated to California. In 1984, Poundstone was cast in the movie Hyperspace but she did not follow through on a potential acting career. Instead she became better known as a comedian and began appearing on several talk shows. In 1989, she won the American Comedy Award for "Best Female Stand-Up Comic".

In 1990, she wrote and starred in an HBO special Cats, Cops and Stuff and subsequently won a CableACE Award for the show. She worked as a political correspondent for the Tonight Show during the 1992 Presidential campaign and did the same for The Rosie O'Donnell Show in 1996.

In 1993, Poundstone won a second Cable Ace Award, began writing a regular column "Hey, Paula!" for Mother Jones magazine (1993-1998), and had a variety show The Paula Poundstone Show on ABC. She was a regular panelist for the game shows Hollywood Squares and To Tell the Truth.