Henning was born in Los Angeles to television Producer Paul Henning and his wife, Ruth. She began to focus on acting in her late teens. Her career began in 1953. Her earliest stage acting roles include: Rebel Without a Cause, Bus Stop, and Gidget. She was cast as a Dancer in the Columbia Pictures film Bye Bye Birdie (1963). She has appeared in numerous musicals including High Button Shoes, Brigadoon, and The Sound of Music.

She made many TV appearances during the 1960s and 1970s on a variety of programs. She appeared in guest roles in network television shows including The Ed Sullivan Show, Adam-12, Happy Days, Mork & Mindy, and The Tonight Show. She also provided the voice of Jethrine Bodine in The Beverly Hillbillies.

Her most notable role was as Betty Jo Bradley in the CBS series Petticoat Junction, which ran from 1963 until 1970. She was only one of three cast members, along with Edgar Buchanan and Frank Cady, to remain throughout the show's entire run and appeared in all but two of the 222 episodes (the exception being the season-one episode "Bobbie Jo and The Beatnik" and the season-two episode "Have Library, Will Travel").

In 1968, a year after Henning's screen marriage to Mike Minor's character in Petticoat Junction, the couple married in real life. They were divorced in 1973 and had no children. Minor's father was Producer Don Fedderson.

She made dramatic appearances in Sliders as Mrs. Mallory, Hunter, and Capitol. Her many game-show appearances include Family Feud, The Match Game, Hollywood Squares, The Perfect Match, Three for the Money, Password, Tattletales, Showoffs, Password Plus, and Body Language. Henning also became a substitute hostess on the 1974–1976 daytime edition of High Rollers.