Greg Behrendt graduated with a Bachelor of Arts degree in theater from the University of Oregon in 1991, though initially he had enrolled to be a business major and play rugby.

After graduation, Behrendt moved to San Francisco, where he joined an improvisational troupe, and met fellow comic Margaret Cho. In his early years, he performed stand-up comedy and improv in San Francisco, California. He was a member of the improv troupe Crash and Burn, whose members included Margaret Cho. He came up as a performer alongside such comics as David Cross (with whom he roomed for years) and Patton Oswalt. .

He went on to appear on The Tonight Show and Late Night with Conan O'Brien. His stand-up special, Greg Behrendt is Uncool, debuted on Comedy Central in January 2006.

In June 2006, he appeared on Celebrity Poker Showdown, playing for a domestic violence charity. Behrendt was a script consultant for the HBO sitcom Sex and the City, "offering script notes from the perspective of a straight man to the writing team, composed of women and gay men".

With Liz Tuccillo, Behrendt co-wrote the 2004 self-help book He's Just Not That Into You. It was adapted by Drew Barrymore's Flower Films/Warner Bros. as a movie of the same name, premiering February 6, 2009.

With his wife Amiira Ruotola-Behrendt, he co-wrote It's Called a Breakup Because It's Broken.

He released the book It's Just a Date! in the U.K. .

His daily daytime "self-help" talk show, The Greg Behrendt Show, premiered September 12, 2006, four months later Sony Pictures Television announced, in January 2007 that the series would not have a second season, and the show aired its last new episodes in February 2007.

He also did a mid-season program for the 2006-07 television season, Greg Behrendt's Wake-Up Call, for ABC, which never aired on the network. The program began airing in January 2009 on ABC's sister cable network SoapNet. He also appeared on the Great Debate at the 2010 Melbourne Comedy Festival, in which he argued as the third speaker for the negative team on the debate "Food is Better Than Sex". Behrendt's team, made up of New Zealand comedienne Cal Wilson, American comedian Russell Kane and Behrendt himself, won the comedy event

He started a podcast "Walking the Room" with his friend Dave Anthony.

He is married to Amiira Ruotula. They have two daughters, Mighty and True. . He is a recovering alcoholic, and as of late 2008 has been sober for 12 years . He plays guitar in his own surf/rockabilly instrumental band, The Reigning Monarchs .He dreams of designing t-shirts.

• Pocket Guide to He's Just Not That Into You: The No-excuses Truth to Understanding Guys, with Liz Tuccillo. Peter Pauper Press, Inc., 2005. ISBN

1593599900.

• It's Called a Breakup Because It's Broken: The Smart Girl's Breakup Buddy, with Amiira Ruotola-Behrendt. Broadway Books, 2006. ISBN 0767921968.
• It's Just a Date: How to Get 'em, How to Read 'em, and How to Rock 'em, with Amiira Ruotola-Behrendt. Harper, 2008. ISBN 0007228325.
• He's Just Not That Into You: The No-Excuses Truth to Understanding Guys, with Liz Tuccillo. Simon & Schuster, 2009. ISBN 141690977X.