She is best known for her roles as receptionist Carol Kester on the 1970s sitcom The Bob Newhart Show, Mrs. Carruthers on Full House, and as the voice of elementary school teacher Edna Krabappel on the animated series The Simpsons, for which she won an Emmy in 1992.

[2] Her father owned and operated Wallace Sundries, a general merchandise store in the typical small rural country Iowa town, where Marcia, her sister Sharon, and brother Jim would often help.

Following her 1960 graduation from Creston High School, Wallace attended nearby Parsons College in Fairfield, Iowa, which had offered her a full scholarship.

[2][3] To make ends meet, she typed scripts, performed in summer stock local theatre, did commercials, and worked as a substitute English teacher in The Bronx in the late 1960s.

[2] After performing for a year in a New York City / Greenwich Village nightclub, Wallace and four fellow entertainer friends formed an improvisational group called The Fourth Wall.

Afterwards, she made several other appearances in improvisational shows,[4] and, after losing 100 pounds (45 kg) from her previous weight of 230,[3] appeared in a nude[3] production of Dark of the Moon at the avant-garde Mercer Arts Center in Greenwich Village (now known as The Kitchen - a performing arts institution relocated to the West Village area of Manhattan).

[2] One of these appearances in March 1972 led to a phone call from TV producer Grant Tinker (husband of comedic actress and fellow producer Mary Tyler Moore), who offered her a supporting role on their new The Bob Newhart Show on the recommendation of CBS-TV founder and longtime chairman William S. ("Bill") Paley.

; Crosswits; Hot Potato; Body Language; The $25,000 Pyramid; Double Talk; Win, Lose or Draw; Tattletales; To Tell the Truth; and Acting Crazy.

Wallace's work onstage included An Almost Perfect Person in Los Angeles which she also produced; a tour of the female version of Neil Simon's The Odd Couple; Same Time, Next Year; Twigs; It Had to Be You; Supporting Cast; Prisoner of Second Avenue; and Plaza Suite.

Other stage productions included Born Yesterday; You're a Good Man, Charlie Brown; Steel Magnolias; and Last of the Red Hot Lovers, in which she played all three female roles at various times.

[3] In 2013, shortly before her death, she voiced the character of the librarian in Monsters University, and in 2014 (posthumously) she portrayed herself in the movie Muffin Top: A Love Story.

She was noted on a list of "Famous Iowans" by her important state capital daily newspaper, the Des Moines Register, in November 2013.

[15] In February 2021, it was announced that archival recordings of Marcia Wallace's voice that she provided as Edna Krabappel would be making a final appearance on The Simpsons.

In an interview with Variety regarding the announcement, Al Jean remarked, "We never got the chance to give sort of a proper goodbye to her in the show, and this is a small attempt to do that.