O'Brien edited a multi-part series on wounded war veterans that won a Pulitzer Prize for National Reporting in 2012.

He helped oversee a team of New York Times reporters that was a 2009 Pulitzer Prize for Public Service finalist for its coverage of the 2008 financial crisis.

O'Brien has written two nonfiction books: 1998's Bad Bet: The Inside Story of the Glamour, Glitz, and Danger of America's Gambling Industry (ISBN 0-8129-2807-5) and 2005's TrumpNation: The Art of Being the Donald (ISBN 978-1422366189).TrumpNation is notable for its claim that celebrity real estate mogul Donald Trump was worth no more than US$250 million.

Trump, who claimed at the time to be a billionaire and who has built a reputation upon his wealth, filed suit against O'Brien and Warner Books in 2006.

In 2019, O'Brien was hired as a senior adviser for strategy and policy for Michael Bloomberg's Democratic Party primaries campaign in the 2020 United States presidential election.