She often played supporting roles as prim, professional women, secretaries, nurses, nuns, therapists, teachers and housekeepers, who made sarcastic quips when the leading characters fell short of her high standards.

Wickes was born to Frank Wickenhauser and his wife, Mary Isabella (née Shannon), in University City which is a suburb of Saint Louis County Missouri on June 13, 1910, of German, Scottish, and Irish extraction, and raised Protestant.

She was accepted into Washington University in St. Louis, where she joined the debate team and the Phi Mu sorority, and she was initiated into Mortar Board in 1929.

A prime example was her deadpan characterization of the harassed housekeeper in the Doris Day vehicles On Moonlight Bay and By the Light of the Silvery Moon, a character type she would repeat in the holiday classic White Christmas (1954), starring Bing Crosby, Danny Kaye, Rosemary Clooney, and Vera-Ellen.

In the 1950s, Wickes played the warm, jocular maid Katie in the Mickey Mouse Club serial Annette and regular roles in the sitcoms Make Room for Daddy and Dennis the Menace.

Wickes also served as the live-action reference model for Cruella De Vil in Walt Disney's One Hundred and One Dalmatians (1961),[6] and played Mrs. Squires in the film adaptation of Meredith Willson's The Music Man (1962).

She was also a regular on the Sid and Marty Krofft children's television show Sigmund and the Sea Monsters and the sitcom Doc.

By the 1980s, her appearances in television series such as Our Man Higgins, M*A*S*H, Columbo, The Love Boat, Kolchak: The Night Stalker, and Murder, She Wrote had made her a widely recognizable character actress.

She was cast as the mother of Shirley MacLaine's character in the film Postcards from the Edge (1990) and portrayed Marie Murkin in the television movie and series adaptations of The Father Dowling Mysteries (1989–1991).

Wickes suffered from numerous ailments in the last years of her life that cumulatively resulted in her hospitalization, where she fell and broke her hip.

[8][9] Her final film role, voicing Laverne in Disney's animated feature The Hunchback of Notre Dame, was released posthumously in 1996.