She became known for appearances in Men Behaving Badly, playing Dorothy, and Jonathan Creek, playing Maddy Magellan. Her early work included appearing on the stage; she was in the chorus of the original cast of Les Misérables.

She has appeared in such series as Whose Line Is It Anyway?, Room 101, Have I Got News For You and the BBC Radio 4 improvisational comedy series The Masterson Inheritance. She also appeared in the telemovie Hot Money, based on the true story of the theft of hundreds of thousands of pounds from the Bank of England. In 1998 came the first sitcom to be built around Quentin herself, Kiss Me Kate. She went on to show her talent for straight acting in Life Begins.

She married fellow BBC comedian Paul Merton in 1990, but they separated in 1997 and were subsequently divorced. With her new partner, Sam Farmer, Caroline had a daughter, Emily, in 1999, and a son, William, in 2003.

At the British Comedy Awards 2004, Caroline Quentin won the "Best Comedy Actress" award for her performance in Von Trapped.