Florence MacMichael began her acting career on Broadway before moving onto radio. When she took the role of Winnie Kirkwood on Mister Ed in 1963, MacMichael had done guest work on such popular television shows as Gunsmoke, My Three Sons, and The Andy Griffith Show.

One of her hobbies was reading cookbooks from all over the world. She didn't actually cook the recipes she read but enjoyed just reading them.