Vangsness got her first big break in the theatre, where she won several awards, including the 15 Minutes of Female Best Actress Award, the Los Angeles Drama Critics Award for Best Emerging Comic Actress, and the Golden Betty Award.
Vangsness says that she is "as queer as a purple unicorn singing Madonna". She began dating film and television editor Melanie Goldstein in 2006. They were engaged, but separated in 2013.
In April 2015, she revealed on smashinginterviews.com that she had entered into a relationship with a new boyfriend and was examining that aspect of her sexuality. In November 2015, it was reported that she was engaged to her boyfriend, actor and writer Keith Hanson.