Her first movie appearance is listed under the name "Yvette Vedder" in Sunset Boulevard (1950), although she was not listed in the production credits. She made her first movie appearance under the Vickers name in Short Cut to Hell (1957), which was directed by James Cagney. In the same year, she starred in American International Pictures' Reform School Girl. Her image was used for the movie's theatrical poster, and it depicted her and Gloria Castillo fighting each other. The poster has subsequently become a collector's item.

In 1953, Vickers married Don Prell, and they were divorced by 1957. Her second marriage was to Leonard Burns in 1959, divorcing in 1961. Her third and final marriage was to Tom Howland from 1967-69. Vickers had no children. She had a long-term relationship with actor Jim Hutton.

She appeared as the Playboy Playmate of the Month in the July 1959 issue. Her centerfold was photographed by Russ Meyer. She also appeared in several other men's magazines. Her film roles began to decrease around this time. She did play some small parts in films from 1962 onward, including a small role in Hud (1963). Her last role was in Evil Spirits, a 1991 horror film.

Vickers was also a singer. In the 1990s, she released a jazz tribute to her parents on CD called A Tribute to Charlie and Maria. In 2005 she visited Canada for the first time to appear at the Toronto Classic Movie Festival. She appears with interviewer Tom Weaver on the audio commentary track of the 2007 DVD release of Attack of the 50 Foot Woman. She had been writing her autobiography before her death.

Vickers was last seen alive in 2010. She had withdrawn from her extended family, and her mummified body was discovered by Actress and neighbor Susan Savage on April 27, 2011, in her 10021 Westwanda Drive, Benedict Canyon, Los Angeles, home. The date of her death is unknown, but forensic Scientists concluded that she may have been dead for as long as a year before her body was discovered. There were no signs of foul play. Vickers was autopsied by the Los Angeles County Medical Examiner, who ruled her cause of death to be heart failure resulting from coronary artery disease. Her remains were cremated.