Parker began ballet training at age 6 and at age 15 she joined a professional dance company. She quit her career in ballet after three years of touring and trained to become an actress while working as a bartender. Her first documented film role was at age 19 in the movie Rented Lips in which she played a dancer/nurse.

Andrea Parker got her break in television playing a nurse on the award-winning Seinfeld episode "The Contest" in 1992. After that first speaking role, she had several other guest-starring roles in television series and movies, most notably a recurring role in ER as Linda Farrell, the love interest of Dr. Doug Ross, and as Caitlin Pike in JAG. She was a body double for Julia Roberts in the movie Pretty Woman; hers are the legs seen in the opening scene of the main character zipping up her boots. She also did several pilots before she gained a cult-following for her role as Miss Parker on the NBC television series The Pretender.

Parker says she felt compelled to play the role of the complex, cynical, powerful and intimidating yet somewhat tortured Ice Queen because her name was "all over the script." Miss Parker is a character many viewers love and others love to hate. Parker also played the minor role of Catherine Parker, Miss Parker's mother in The Pretender, a role that is in stark contrast to the character Miss Parker.

After The Pretender was cancelled by NBC in 2000, Parker did another guest spot on JAG before signing on to reprise her role as Miss Parker in the telemovies for The Pretender, which aired on TNT in 2001. She then returned to series television in 2002 and starred in the ABC network comedy Less Than Perfect, playing Lydia Weston until it was cancelled in 2006. She has made several guest appearances on television talk shows and celebrity events such as the various celebrity poker tournaments.

Parker is noted for her support of various charities such as the National Hospice Palliative Care Organization, Glenn Siegel's My Good Friend charity organization, The Michael J. Fox Foundation for Parkinson's research and Project Angel Food. Parker is also trained as a stunt-driver and can handle firearms.