San Giacomo was born in New Jersey and attended Washington College and the Carnegie Mellon School of Drama. She has appeared in the films Miles from Home (1988), Sex, Lies, and Videotape (1989), Pretty Woman (1990), Quigley Down Under (1990), and Nina Takes a Lover (1994), among others. She was the lead character as the neo-feminist Maya Gallo in the sitcom Just Shoot Me (1997-2003) and did voice work for the animated series Gargoyles as the character of Fox, but for some reason, her name does not appear in the ending credits with the rest of the cast. She was to have made her return to television on The WB's new drama Related in 2005, but the character she was to play was recast due to creative differences. Laura made her first public appearance in nearly a year on October 19, 2005. Laura made an appearance at the 15th Annual Environmental Media Awards.
She also appeared in the Stephen King TV miniseries The Stand, playing the part of Nadine Cross.
San Giacomo has been married twice; to actor Cameron Dye (1990-1998), with whom she has a son, Mason (born 1996), and to actor Matt Adler (since 2000). She is the cousin of Torry Castellano, a member of the rock group The Donnas.