Born Emogeane Coca in Philadelphia, Coca was the daughter of Joseph Fernandez Coca, a violinist and vaudeville orchestra conductor, and Sadie Brady, a dancer and magician’s assistant. Coca’s father was of Spanish descent (the family surname was originally Fernández y Coca), the son of Joseph F. Coca, Sr., and his wife, Laura. Coca took lessons in piano, dance, and voice as a child and while still a teenager moved from Philadelphia to New York City to become a dancer. She got her first job in the chorus of the Broadway musical When You Smile, and became a headliner in Manhattan nightclubs with music arranged by her first husband, Robert Burton. She gained prominence when she began to combine music with comedy; her first critical success was in New Faces of 1934. A well-received part of her act was a comic striptease, during which Coca made sultry faces and gestures but would manage to remove only one glove. She committed this routine to film in the Educational Pictures comedy short The Bashful Ballerina (1937), and co-starred opposite another newcomer to films, Danny Kaye, in Educational’s 1937 short Dime a Dance. Both of these comedies were filmed in New York. She played opposite Sid Caesar on The Admiral Broadway Revue (January to June 1949), and then in the sketch comedy program Your Show of Shows, which was immensely popular from 1950 to 1954, winning the Emmy for Outstanding Variety Series in 1952 and 1953. The 90-minute show was aired live on NBC every Saturday night in prime time. She won the second-ever Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series in 1951 and was nominated for four other Emmys for her work in the show. She was also singled out to win a 1953 Peabody award for excellence in broadcasting. Her success in that program earned her her own series, The Imogene Coca Show, which ran from 1954-55.

Prior to working with Caesar she had starred in an early ABC series, Buzzy Wuzzy, which lasted four episodes in 1948. She went on to star in two more series. In the 1963–64 TV season, Coca portrayed a comic temporary helper in the NBC sitcom Grindl. It competed with the second half of The Ed Sullivan Show and lasted only one season. Coca later starred as a cave woman with Joe E. Ross in the 1966–67 time-travel satire sitcom It’s About Time. She continued to appear on comedy and variety series throughout the 1950s, ’60s, ’70s and ’80s including several appearances each on The Carol Burnett Show, The George Gobel Show, The Hollywood Palace and Ed Sullivan’s Toast of the Town, and Bob Hope specials. She appeared on other shows and specials by Dean Martin, Jackie Gleason, Jerry Lewis, Dick Clark, Danny Kaye, and Andy Williams. The Sid Caesar, Imogene Coca, Carl Reiner and Howard Morris Special won a 1967 Emmy for Outstanding Variety Special. She made memorable guest appearances on sitcoms including two appearances on Bewitched, The Brady Bunch, and Mama’s Family. She appeared with Milton Berle and Your Show of Shows co-star Howard Morris in “Curtain Call”, a 1983 episode of Fantasy Island.

Coca appeared in a number of literary adaptations for children. In 1960 she was Miss Clavel in Sol Saks’ adaptation of Ludwig Bemelmans’ Madeline for Shirley Temple’s Storybook. In 1972 she voiced the character of Princess Jane Klockenlocher in a Rankin/Bass version of Hans Christian Andersen’s The Emperor’s New Clothes. In 1978 she appeared in A Special Sesame Street Christmas. In 1985, she played The Cook in Alice in Wonderland, an all-star TV miniseries adaptation of the book by Lewis Carroll. Among her final roles was voicing characters in Garfield and Friends. In 1988 Coca appeared as the mother of Allyce Beasley’s Agnes in the Moonlighting episode “Los Dos Dipestos”, written by David Steinberg. She received her sixth Emmy nomination, as Outstanding Guest Performer in a Drama Series, for the role. The same year she was the female recipient of the Lifetime Achievement Award in Comedy at the second annual American Comedy Awards, alongside male recipient George Burns. Coca appeared only sporadically in films such as The Incredible Incident at Independence Square, filmed in her hometown of Philadelphia, as well as Under the Yum Yum Tree (1963), Nothing Lasts Forever, Papa Was a Preacher, Buy & Cell, and National Lampoon’s Vacation (1983), as “Aunt Edna”.

After having appeared in several Broadway musical-comedy revues and plays between the 1930s and the 1950s, Coca returned to Broadway at the age of 70 with a Tony Award-nominated performance as religious zealot Letitia Primrose in On the Twentieth Century, a 1978 stage musical adapted from the 1934 film Twentieth Century. Her role, that of a religious fanatic who plasters decals onto every available surface, had been a male in both the film and the original stage production, and was rewritten specifically as a vehicle for Coca.[citation needed] She appeared in the Broadway run with Kevin Kline and Madeline Kahn, continued with the national tour starring Rock Hudson and Judy Kaye, and returned for a later tour revival in the mid-1980s with Kaye and Frank Gorshin. She also co-starred with singer Maxine Sullivan in My Old Friends and touring productions including musicals such as Once Upon a Mattress and Bells Are Ringing and plays such as The Prisoner of Second Avenue and Luv. She rejoined Sid Caesar in 1961–62, 1977 and 1990–91 for a traveling stage revue, and made an appearance with Caesar and Howard Morris at Comic Relief VI in 1994. One of Coca’s early stock characters on the Caesar series blended comedy with socially conscious pathos as a bag lady, and she was frequently asked to reprise the role, including by Carol Burnett for her 1960s series and by Red Skelton as love interest to one of his own familiar characters in the 1981 TV special Freddie the Freeloader’s Christmas Dinner. New wave group Ēbn-Ōzn featured Coca as the title character in the music video to their song “Bag Lady (I Wonder)”, which was a top-40 dance hit in 1984.