Born in Oak Park, Illinois, Mansfield was a moppet radio star in Chicago, Illinois. Her father gave her the nickname "Sally". As a youth she joined the Actors Company of Chicago and the Children's Summer Theatre and studied at the Sherwood Music School. Coming to New York City in 1945, she voiced several radio roles for commercials and on soap operas and dramas. As a chorine with the Don Arden Dancers, she performed in revues in New York and in Las Vegas.

Mansfield appeared on many popular TV shows in the 1950s and 1960s, including Death Valley Days, The Donna Reed Show, and The Andy Griffith Show, and The Phil Silvers Show and was a regular on Bachelor Father. She was also an accomplished Dancer, performed with the Don Arden Dancers in New York City and Las Vegas, and entertained US troops in Korea.

Moving to Hollywood, Mansfield met up with a talent scout for Paramount Pictures while she was in the Geller Workshop. She landed a bit part in Forever Female (1953) as the secretary of Paul Douglas. She was a regular on the CBS Gunsmoke radio show in 1954.

She is perhaps best remembered, however, for her 1954 role as spaceship navigator "Vena Ray" on the science fiction CBS-TV show Rocky Jones, Space Ranger. She was chosen from 300 who auditioned. Her character anticipated Nichelle Nichols' much more famous role as a female spaceship bridge officer on the 1960s television series Star Trek. The same year Mansfield carried the Miss Emmy torch at the Palladium during the sixth annual Academy of Television Arts & Sciences awards banquet.

Mansfield gained notoriety for modeling a sweater designed by Edith Head, which she wore when she entertained U.S. Army troops in Alaska and Japan. The sweater's back was padded with heat-producing chemicals, and this then-novel idea along with Mansfield's photo was widely syndicated. She modeled a two-piece bathing suit in Pose! The Picture Magazine, in March 1955.

Sally Mansfield died of lung cancer in California in 2001 at the age of 80.