Laura San Giacomo was born in New Jersey and attended Washington College and the Carnegie Mellon School of Drama. She has appeared in such films as Miles from Home (1988), Sex, Lies, and Videotape (1989), Pretty Woman (1990), Quigley Down Under (1990), and Nina Takes a Lover (1994).

San Giacomo played the lead character, the neo-feminist Maya Gallo, in the sitcom Just Shoot Me (1997-2003), and has since done voice work for the animated series Gargoyles (as the character of Fox), although her agent insisted that her name not appear in the ending credits. She also appeared in the Stephen King TV miniseries The Stand, playing the part of Nadine Cross.

She was to have made her return to television on The WB's new drama Related in 2005, but the character was recast due to creative differences.

Laura made her first public appearance in nearly a year on October 19, 2005, at the 15th Annual Environmental Media Awards.

San Giacomo has been married twice; to actor Cameron Dye (1990-1998), with whom she has a son, Mason (born in 1996) who suffers from cerebral palsy, and to actor Matt Adler (since 2000). She is a cousin of Torry Castellano of the rock group The Donnas.