Stapleton originated role in the stage musicals "Damn Yankees" and "Bells Are Ringing" which she reprised for the feature film versions in 1958 and 1960 respectively. She was also seen in "Woman With a Past," a short-lived 1954 TV series, as well as in episodes of "Dr. Kildare," "The Defenders" and "Naked City." But ask anyone in America prior to 1971 if they knew the name "Jean Stapleton", and only the most avid theater groupie or film trivia nut would have been able to answer. Stapleton seemed no worse for the lack of attention, working steadily and raising two children. Then came Norman Lear who was fond of casting stage players in TV. Stapleton had appeared in Lear's feature "Cold Turkey" (shot in 1969; released in 1971) and he offered her what became her signature role: Edith Bunker. The character was meant to be the voice of truth to husband Archie Bunker, the bigoted loading dock American man pained by changes in the world and set upon by his liberal, live-in son-in-law. But Stapleton brought a humanity to the role not foreseen by Lear and his writers. While seen mostly twirling ripostes in the pilot episode, Edith Bunker rose to assuage Archie's tempers, while carving out a life as a warm, friend-to-all. While Archie called her "dingbat" because she was not too smart (or at least, worldly), Edith nevertheless joyfully and dutifully charged out of her kitchen each evening at his return from work with a squealing cheery, "Hi, Archie. How was your day?" followed by a big kiss Archie always could have done without. But Edith was more than just support. The character was molested, went through menopause, found her own voice, and in many ways adapted to the new world better than her husband. Perhaps she couldn't ace the SATs, but Edith had horse sense and heart. Following the departure of Sally Struthers and Rob Reiner from "All in the Family", Stapleton agreed to be appear regularly but not weekly on "Archie Bunker's Place", the sequel series. After one season, she had tired of the role, and the 1980 season began with Archie mourning the death of Edith a few months before. Stapleton had not given America a death scene, but the nation mourned.

Stapleton, who for years had been "the other Stapleton" behind the unrelated Maureen, now was a household face. She continued appearing on stage at the Totem Pole Theatre during summers, and starred in several TV-movies, principally as "Aunt Mary" (CBS, 1978), an embittered old woman who becomes coach of a little league team, and "Eleanor: Woman of the World" (CBS, 1982), about life after Franklin Roosevelt's death. She also appeared in the occasional feature, including "Up the Down Staircase" (1967), "Klute" (1971), "The Buddy System" (1984) and Nora Ephron's "Michael" (1996). In the latter, Stapleton portrayed a feisty senior citizen who sheltered a visiting angel (John Travolta).

In 1984, Stapleton was offered the lead role in a proposed CBS series about a teacher turned mystery writer, but despite announcements in trade publications, she turned down "Murder, She Wrote". Her TV appearances became less frequent in the late 80s, but she continued to appear on stage, sometimes on Broadway, such as in a 1986 revival of "Arsenic and Old Lace", sometimes off-Broadway, as in a 1989 OBIE-winning turn in "The Birthday Party". Stapleton attempted a return to sitcoms co-starring with Whoopi Goldberg in the short-lived "Bagdad Cafe" (CBS, 1990). She also starred in the TV-movie "Ghost Mom" (Fox, 1993), played the title role in the Showtime cable series "Mrs. Piggle-Wiggle" (1994), and made a memorable appearance as Miles Silverberg's aunt in an episode of "Murphy Brown" (CBS, 1996).