She may be best known for her portrayal of the long-suffering, yet devoted wife and mother Edith Bunker on the popular and groundbreaking 1970s sitcom All in the Family, and occasionally in the sequel Archie Bunker's Place. Her awards for the show include three Emmys and three Golden Globes.

She began her New York career Off-Broadway in American Gothic. She has been featured on Broadway in several famous musicals (Damn Yankees, Bells Are Ringing, Juno) and in many other stage productions.

She has also acted in made-for-TV movies and feature films such as Klute, which starred Jane Fonda and Donald Sutherland, and Cold Turkey, which starred Bob Newhart. She also had a recurring role on TV's Scarecrow and Mrs. King as an English spy. Stapleton appeared in the 1999 movie You've Got Mail. She played Birdie Conrad, a friend of Meg Ryan's character's mother.

Her husband, William H. Putch, by whom she had 2 children, actor/writer/director John Putch and actress Pamela Putch, died in 1983. She had been dating comic actor Howard Morton until he died of a stroke in 1997.

Stapleton is not related to Maureen Stapleton; she acquired her professional name of Jean Stapleton as so many other actors have done, by using her mother's maiden name. Jean Stapleton has numerous relatives in show business, including actress cousin, Betty Jane Watson (born in 1921), who appeared on Winner Take All (1951).