[1] Her mother, Dolores Dee Azzara, is of Sicilian ancestry (Villabate) and her father, Sam Parrilla, is a Puerto Rico-born baseball player who played one season with the Philadelphia Phillies.

After that she joined Donnie Wahlberg and Neal McDonough in the short lived crime drama Boomtown, for which she received the Imagen Award for Best Supporting Actress,[6] for her portrayal of Teresa, a paramedic.

Initially a success, Boomtown began to struggle, and Parrilla's character became a police academy rookie, to tie her more closely to the rest of the show.

Parrilla guest-starred in a number of television dramas, including JAG, Six Feet Under, Covert Affairs, Medium, The Defenders and Chase.

In 2007, she guest starred as Greta during the third season of ABC's Lost in the episodes "Greatest Hits" and "Through the Looking Glass" In 2008, she had a leading role in the Lifetime film The Double Life of Eleanor Kendall, in which she played Nellie, a divorcee whose identity has been stolen.

In 2010, Parrilla had a female lead role in the Jerry Bruckheimer-produced Miami Medical on CBS, which had a short run towards the end of the 2009–10 television season before it was canceled in July 2010.

In February 2011, she was cast as Mayor Regina Mills/The Evil Queen, in the ABC adventure fantasy drama Once Upon a Time, created by Edward Kitsis and Adam Horowitz.

In 2012 and 2013, she was regarded as a promising contender for an Emmy Award in the Outstanding Supporting Actress in a Drama Series category,[11][12][13][14][15][16] though she did not receive a nomination.