- Lucille Ball as Lucille Esmeralda "Lucy" McGillicuddy-Ricardo
- Desi Arnaz as Enrique Alberto "Ricky" Ricardo y de Acha III
- Vivian Vance as Ethel Roberta Mertz
- William Frawley as Frederick Hobart "Fred" Mertz
- Keith Thibodeaux as Richard Robert Ricardo ("Lil' Ricky")
Main Cast Members
Extras Cast throughout the series
- Kathryn Card as Mrs. McGillicuddy -- Lucy's Mom
- Frank Nelson as Ralph Ramsey
- Mary Jane Croft as Betty Ramsey
- Jerry Hausner as himself
- Bob Jellison as Bobby "Robert"
- Doris Singleton as Carolyn Appleby
- Shirley Mitchell as Marion Strong
- Elizabeth Patterson as Mrs. Matilda Trumbull
- Joseph D. and Michael Mayer as Ricky Ricardo, Jr.
- Richard and Ronald Lee Simmons as Ricky Ricardo, Jr.
- Charles Lane as various characters
- Barbara Pepper as various characters
- Bob Smith as various characters
- Gale Gordon and Bea Benaderet, supporting cast members on My Favorite Husband, were originally approached for the roles of Fred and Ethel, but neither could accept due to previous commitments. Gordon did appear as a guest star in three episodes, playing Ricky's boss, Mr. Littlefield, in two episodes, and later in an hour-long episode as a civil court judge. Gordon was a veteran from the classic radio days in which he perfected the role of the exasperated character, as in Fibber McGee and Molly and Our Miss Brooks. He would go on to co-star with Ball in most of her post–I Love Lucy series. Benaderet was a guest star in one episode as the Ricardos'
neighbor, the elderly Miss Lewis.
- Barbara Pepper (later featured as Doris Ziffel in the series Green Acres) was also considered to play Ethel, but Pepper had been drinking very heavily after the death of her husband, Craig W. Reynolds. Her friendship with Ball dated back to the film Roman Scandals, in which both appeared as Goldwyn Girls. She turned up regularly in bit parts.
- Lucille Ball liked naming supporting characters after real-life people. For instance, Carolyn Appleby had been one of her teachers, and Marion Strong was a friend in Jamestown, New York.