Silo was born in New York City, New York. Her acting career started in television on an episode of The Jack Benny Show. She also co-starred with Larry Blyden, Dawn Nickerson, and Diahn Williams in the NBC sitcom Harry's Girls, about a vaudeville troupe touring Europe. She also made guest appearances in episodes of numerous 1960s TV series, including Route 66, The Many Loves of Dobie Gillis, The Man from U.N.C.L.E., and many more. She also appeared as Rita Lane on Gunsmoke in 1969.
Susan Silo began her voice-acting career as a talking cow in a series of Land O' Lakes Margarine commercials for over ten years. She has done voices for Hanna-Barbera, Marvel, Disney, Ruby-Spears, DIC, Film Roman, and Murakami Wolf Swenson, among others.