Gutfeld was born and raised in San Mateo, California. He attended Junípero Serra High School and the University of California, Berkeley, graduating in 1987.

Gutfeld currently resides in New York City with his wife, Elena Moussa, whom he met in London.

After graduating from UC Berkeley with a degree in English, he interned at The American Spectator, as an assistant to R. Emmett Tyrrell. He then got his first full-time job as a staff writer at Prevention magazine. In 1995, he became a staff writer at Men's Health.

He was promoted to editor-in-chief of Men's Health in 1999. In 2000, he was replaced by David Zinczenko and became editor-in-chief of Stuff. At Stuff, he increased the circulation from 750,000 to 1.2 million. In 2003, he hired several midgets to attend a conference of the "Magazine Publishers of America" on the topic of "buzz," with the instructions to be as loud and annoying as possible. The stunt did generate publicity for Stuff; but, it led to Gutfeld being fired from the magazine soon afterward; he was then made head of "brand development" at Dennis Publishing.

He helmed Maxim magazine in the UK, from 2004 to 2006. However, Gutfeld's contract expired without renewal after losses in readership under his tenure. His final year at Maxim saw a loss of about 40,000 readers. On the December 16, 2009 episode of Red Eye w/ Greg Gutfeld, Gutfeld's former boss, Maxim owner Felix Dennis, stated that Gutfeld was fired as a result of a Maxim story entitled "The Ikea Sex Party", for which the publication was sued.

Gutfeld was a contributor to the website The Huffington Post from its launch until October 2008; frequent targets of his sarcasm include his Huffington Post colleagues Deepak Chopra, Cenk Uygur and Arianna Huffington. Many of his Huffington Post commentaries/blogs are still available on its website.[1] He currently blogs at his own site, "The Daily Gut."

Since February 5, 2007, Gutfeld has been host of the hourlong Fox News Channel late-night program, Red Eye w/Greg Gutfeld, which airs at 3 AM Eastern Time. Gutfeld's "sidekick" on Red Eye since the show began, Bill Schulz, is a former colleague of Gutfeld's from Stuff magazine.

In August 2010, Gutfeld made news by proposing to start a gay bar for Muslims in New York City next door to the planned Park51 Mosque, sometimes referred to as the "Ground Zero mosque".