Jean Vander Pyl was born in Philadelphia to John H. and Kathleen Hale Vander Pyl. Her grandfather had come from the Netherlands. Her father was the district manager for Knit Underwear, her mother was a Southerner from Tennessee. The two died within six months of each other in the early 1950s. The family came to Los Angeles by the mid-1930s.

Most of her other voice acting work was also for the Hanna-Barbera studio, where she played her first voice role in 1958 on an episode of The Huckleberry Hound Show, voicing an Actress in The Yogi Bear episode, "Show Biz Bear". She did additional voices, particularly Southern belles and beautiful girls, on The Quick Draw McGraw Show, Snagglepuss and The Yogi Bear Show. In 1961-62, Vander Pyl played Nurse Larue, Charlie the baby, Goldie, Lola Glamour and additional voices on multiple episodes of Top Cat and in 1962, she did another memorable role, as Rosie, the Jetsons' robotic maid, and 23 years later in 1985 she reprised the character on the returning series.

On radio she was heard on such programs as The Halls of Ivy (1950–52) and on Father Knows Best during the early 1950s, where she portrayed Margaret Anderson; the role was played on television by Jane Wyatt. Her husband, Carroll G. O'Meara, died on February 18, 1962, at age 53. He was a graduate of Stanford University who worked as a copywriter at KHJ radio in the mid-1930s and later became an advertising executive. She later married Roger Wells DeWitt, who also predeceased her.

Later, she did the voices of Maw Rugg and her daughter Floral Rugg on a rural cartoon, The Hillbilly Bears and Winsome Witch; both shows were part of The Atom Ant/Secret Squirrel Show (1965–1967). Jean Vander Pyl was also the voice of Little Ogee on The Magilla Gorilla Show. In 1969, Vander Pyl guest starred on the Scooby-Doo, Where Are You! episode "Foul Play in Funland", playing Sarah Jenkins.

In the 1970s, she was the voice of Marge Huddles, the main character's wife on Where's Huddles?, in which she played a role similar to that of Wilma Flintstone and was reunited with her Flintstones cast members Alan Reed and Mel Blanc. She went on to voice Mrs. Finkerton on Inch High, Private Eye, as well as several female characters on Hong Kong Phooey, The Tom and Jerry Show and Captain Caveman and the Teen Angels.

In the 1980s and 1990s, the talented voice Actress did voices on Mister T, Snorks, Yogi's Treasure Hunt and also on The Flintstone Kids as Mrs. Slaghoople. She mostly reprised Wilma Flintstone on spin-off series and films such as The Flintstone Comedy Hour, The New Fred and Barney Show, The Flintstone Comedy Show, The Jetsons Meet the Flintstones, I Yabba-Dabba Do!, Hollyrock-a-Bye Baby, and A Flintstones Christmas Carol.

Vander Pyl made numerous TV appearances as an Actress in programs such as Leave It to Beaver, The Donna Reed Show, Father Knows Best, The Beverly Hillbillies, That Girl, and Petticoat Junction. One of her final TV appearances was in the opening scene of the Season Two Murder, She Wrote episode, "One Good Bid Deserves a Murder". Vander Pyl also had a very brief cameo appearance in the 1994 live-action film version of The Flintstones as Mrs. Feldspar, an elderly woman in a conga line.

Her last roles were again as Wilma Flintstone on What a Cartoon! episode "Dino: Stay Out!" in 1995, A Flintstone Family Christmas in 1996 and on The Weird Al Show in 1997.

On April 10, 1999, Vander Pyl died of lung cancer at her home in Dana Point, California. She was 79 years old. She was survived by her three sons, Michael and Timothy O'Meara, and Roger DeWitt, Jr. DeWitt, Jr. is also an actor and singer. Her daughter, Tina O'Meara, died in the 1970s. Vander Pyl was interred in Ascension Cemetery in Lake Forest, California. Her most prominent character Wilma Flintstone is engraved on her gravestone.