Annie Duke was born in Concord, New Hampshire where her father, Richard Lederer, a writer and linguist, was teaching at St. Paul's School. Her brother Howard Lederer also became a poker pro; her sister Katy Lederer is an author and poet. Annie Duke went to Columbia University where she double majored in English and psychology.
Annie Duke was awarded a NSF Fellowship to attend graduate school at the University of Pennsylvania to study cognitive psychology, specifically psycholinguistics. Her intention was to become a professor but Annie Dukeshe left school in 1992, after five years of graduate school and one month before defending her Ph.D. work. She left academia to pursue family life with her husband, Ben Duke, and moved to Columbus, Montana.
While living in Montana, Duke began playing poker in the legal card rooms in Billings. In 1994, she and her husband moved to Las Vegas in support of her decision to start playing poker full time. Prior to 2004, her main claim to poker fame was her 10th place finish in the 2000 World Series of Poker main event (one position short of the final table) while eight months pregnant with her third child.
In early 2004, Duke received considerable publicity because she tutored actor Ben Affleck in poker, who went on to win the 2004 California State Poker Championship. In September 2004 Duke won $2,000,000 in the inaugural World Series of Poker Tournament of Champions, a 10-player, winner-take-all invitational event. She subsequently appeared on the David Letterman show.
Today Duke is regarded as one of the best female poker players. As of 2005, Duke has won one World Series of Poker bracelet, in Omaha HiLo and more than $3.1 million in tournament play. Nowadays she refuses to play in women's only tournaments, saying that “Poker is one of the only sports where a woman can compete on a totally equal footing with a man, so I don't understand why there's a ladies only tournament.” 
Duke is one of many poker players that take issue with the restrictions placed on players during televised tournaments. Although the players pay mandatory entry fees to enter tournaments, some venues do not allow players to wear sponsorship logos. Duke raised some controversy when she made a statement in a news article regarding this issue: “We [poker players] are not even slaves. We're people paying to pick the cotton.”
Duke has been a spokesperson for Ultimate Bet since 2000 and has written many articles for the online poker website, mainly on Omaha HiLo. She has several nicknames including “Annie Legend”, “The Duke”, and “The Duchess of Poker”. Her sister, Katy Lederer, wrote a book about the Lederer family, titled Poker Face: A Girlhood Among Gamblers. She also has her own biography, called Annie Duke: How I Raised, Folded, Bluffed, Flirted, Cursed, and Won Millions at The World Series of Poker (ISBN 1594630127). In promotion of her book she appeared on Comedy Central's The Colbert Report in an episode that originally aired on January 30th, 2006.
In 2002 she moved to Portland, Oregon to work for ieLogic, a company that produces software for online real time casino gaming. She and Ben were divorced in 2004. In 2005 she and her four children moved to the Hollywood Hills neighborhood of Los Angeles, California. Her new Mediterranean-style home and boyfriend, actor and producer Joe Reitman, were featured in the New York Times article AT HOME WITH: ANNIE DUKE; Dealt A Bad Hand? Fold 'em. Then Raise. on January 19, 2006.
In 2005 Duke helped her brother Howard Lederer promote a line of poker video games which featured both siblings as virtual characters.