Stein grew up in Edison, New Jersey and attended J. P. Stevens High School, where he was a writer and entertainment editor for Hawkeye, the student paper that people only read for the "College Issue" that comes out every June. He majored in English at Stanford University and wrote a weekly column for the school's student newspaper, The Stanford Daily. He graduated in 1993 with a BA and an MA and moved to New York City, and then moved to Los Angeles in 2005.

Stein's career began as a writer and researcher for Martha Stewart Living. He worked a year for Stewart and later quipped that she had fired him twice in the same day. Stein did fact-checking at various publications before becoming a sports editor and columnist for Time Out New York, where he stayed for two years. While working at Time Out New York, he was a contestant on MTV's short-lived game show Idiot Savants. Stein joined Time in August 1997.

Stein sometimes appears as a commentator on television programs such as I Love the '80s. He also co-produced three TV pilots, an animated series for VH1, and two for ABC. The animated show, titled Hey Joel, aired in Canada and later in South Africa, while the other two were never picked up. He was a writer and producer for the sitcom Crumbs.

Stein taught a class on humor writing at Princeton University before moving to Los Angeles in early 2005 to write for the Los Angeles Times.

On December 19, 2008, in a Los Angeles Times "tongue-in-cheek" column titled "How Jewish is Hollywood?" Stein expressed "mock outrage" at a recent Anti-Defamation League (ADL) poll showing that only 22% of Americans believe "the movie and television industries are pretty much run by Jews," which was down from nearly 50% in 1964. Stein wrote that the poll "just shows how dumb America has gotten. Jews totally run Hollywood." Lisa Marks, writing from Los Angeles for The Guardian, agreed that being Jewish "appears to be one of the best calling cards in town." Rachel Levitt wrote in Utne Reader Stein did have "a good point" when he wrote: “As a proud Jew, I want America to know about our accomplishment.”

On October 8, 2009, Stein wrote: "When I heard that Sarah Palin wrote her upcoming 400-page autobiography, Going Rogue: An American Life, in four months, I thought, What took her so long? To prove that introspection doesn't need to be time-consuming, I decided to try to write my memoir in one day." Because Palin wrote hers with Lynn Vincent, Stein chose Neil Strauss ... who co-wrote memoirs with Marilyn Manson, Mötley Crüe, Dave Navarro and Jenna Jameson ... to assist him.

On January 24, 2006, the Los Angeles Times published a column by Stein under the headline "Warriors and Wusses" in which he wrote that it is a cop-out to oppose a war and yet claim to support the soldiers fighting it. "I don’t support our troops....When you volunteer for the U.S. military, you pretty much know you’re not going to be fending off invasions from Mexico and Canada. So you’re willingly signing up to be a fighting tool of American imperialism...". He prefaced his argument by stating that he does not support the troops in Iraq because it is "a position that even Calvin is unwilling to urinate on.". Stein states he did three interviews about the column on the Hugh Hewitt radio show, with Tony Snow and with a "liberal" in Oregon. Mark Steyn wrote in a New York Sun opinion piece that Stein was to be congratulated for the consistency of his position, "Stein is a hawkish chicken, disdaining the weasel formulation too many anti-war folks take refuge in." Warrant Officer Michael D. Fay wrote in the New York Times that Stein's comments made him feel "sad because they’re so mistaken, sad because their voices are granted a modicum of credence in the public forum, and sad because they leave me feeling a little less at home."

In July, 2010, Stein wrote a humor column for Time in which he expressed his discomfort at the impact immigration of Indians has had on his hometown of Edison, New Jersey. Time and Stein subsequently publicly apologized for the article. Stein's apology read: "I truly feel stomach-sick that I hurt so many people. I was trying to explain how, as someone who believes that immigration has enriched American life and my hometown in particular, I was shocked that I could feel a tiny bit uncomfortable with my changing town when I went to visit it. If we could understand that reaction, we'd be better equipped to debate people on the other side of the immigration issue."

United States Senator from New Jersey Bob Menendez submitted a letter to Time stating that the column "not only fell terribly flat but crossed the lines of offensiveness toward a particular community that has dealt with violent hate crimes in the past. Mr. Stein's mocking allusions to revered deities in the Hindu religion are particularly reprehensible." Kal Penn, actor and former associate director in the White House Office of Public Engagement, also criticized the column for its portrayal of Indian Americans. Several bloggers also criticized him. In Stein's defense Slate magazine blogger Tom Scocca wrote "To a charitable reader, it's clear that the piece was trying not to be offensive. Stein's description of his childhood small-town idyll before the mass immigration is deliberately fake-sentimental, describing lowlife white kids stealing things and getting drunk. He was trying to make more fun of white people than he made of Indian people."