She was born Imogene Fernandez de Coca in Philadelphia, Pennsylvania, of Spanish and Irish extraction as the daughter of José Fernandez de Coca, a conductor, and his wife Sadie Brady, a dancer and magician's assistant.

In her youth, she received piano, dance, and voice lessons. She moved from Philadelphia to seek a living as a dancer, while still a teenager, starting in the chorus of the Broadway musical When You Smile. She came to be featured as a headliner, appearing in Manhattan nightclubs, with music arranged by her first husband, Robert Burton. She came to prominence when she began to combine music with comedy: her first big critical success was in New Faces of 1934.

In the early days of live television she played opposite Sid Caesar in a sketch comedy program, Your Show of Shows, which was immensely popular from 1950 to 1954. She also had, briefly, her own series, The Imogene Coca Show. Her first husband, Robert Burton, died in 1955.

In 1960 she married her second husband, late actor King Donovan.

She made one final performance on the Broadway stage as religious zealot Letitia Primrose in On the Twentieth Century, and was nominated for a Tony Award. Her later years were spent in relative solitude with only occasional appearances guest-starring on television (Moonlighting) and in small movie roles.

She died, childless, in Westport, Connecticut of Alzheimer's disease and natural causes at the age of 92.