Born c. 1984/1985, Holzhauer was born and raised in Naperville, Illinois. His father was a German immigrant. His grandmother was Japanese and spoke very little English; he had promised her that he would appear on Jeopardy! before she died. In 1989, when he was four, his teacher was astounded by his arithmetic abilities and developed advanced classwork just for him. At age seven, he was moved up to a fifth-grade math class, and at his mother’s urging he skipped second grade. He consistently got A’s on math tests and competed on the Naperville North High School math team.

During his 33 appearances, Holzhauer exceeded Craig’s single-day total 16 times (see table below), including a new all-time record set on April 17, when he won $131,127. He is also the first and only player to win $100,000 or more in a single episode, a feat he accomplished six times. His $298,687 total winnings across his first five days surpassed the five-day record set by Frank Spangenberg in 1990 before the changes in the values of the clues. Holzhauer is the only contestant to date to do so. Holzhauer won a total of $2,464,216, averaging $75,362 per episode—a 33-day average that nearly equaled the previous all-time single-day record.

The highest-rated episode during Holzhauer’s run was his final one, which at 14.5 million same-day viewers was the highest-rated episode since Jennings’s last episode in 2004, the highest-rated episode of a syndicated show that season and the third-most-watched episode of a running series in the 2018–19 season (behind only the series-ending “The Stockholm Syndrome” episode of The Big Bang Theory and an episode of 60 Minutes that had led out of an NFL on CBS contest), not counting DVR or streaming views, the latter of which Jeopardy! does not offer. The episode had been spoiled several hours before it aired on most affiliate stations; Sports Illustrated credited the spoilers with creating buzz, counteracting the conventional wisdom that people would not tune in without the element of surprise. Even if the result had not been spoiled, Holzhauer was on pace to break Jennings’s regular-play record that day had he won, which might also have had a part in the increased ratings.

Holzhauer was a member of the Worldwide Youth in Science and Engineering Team that won the state competition at the University of Illinois at Urbana–Champaign; he contributed by taking first place in physics and second in math. He graduated with a Bachelor of Science degree in mathematics in 2005.

While a student at the University of Illinois at Urbana–Champaign, Holzhauer played hearts and spades at a card club. The twice-a-week club quickly turned into a five-day-a-week home poker game with a 10-cent ante and $2 maximum bets. The poker game is where Holzhauer began gambling but he grew his sports betting bankroll in the 2006 World Baseball Classic. Believing the round-robin format of the tournament and variance in baseball had skewed the odds, he bet heavily on each team except the US and the Dominican Republic to win the tournament. After graduating from college, Holzhauer moved to Las Vegas in 2008 to bet professionally on sports. Holzhauer says he has built predictive models for baseball, NFL, and college basketball, but now focuses largely on in-game betting.

On September 8, 2012, Holzhauer married Melissa Sassin, a tutor from Seattle, Washington. Sassin has also been a game show contestant, appearing on Who Wants to Be a Millionaire in 2014 and winning $28,800. Their daughter, Natasha, was born on November 9, 2014.

Holzhauer appeared on the American version of the quiz show The Chase on September 2, 2014, internationally produced by ITV Studios. In his first round, a one-minute round called the Cash Builder, he correctly answered 12 questions out of 13 posed by host Brooke Burns; the last question was asked just before time expired and was quickly passed on by Holzhauer. His score set a record for the Cash Builder that was never surpassed during the show’s run.

Holzhauer appeared on the American quiz show 500 Questions on May 22, 2015. This show did not allow the challenger to replace the champion unless the champion answered three questions wrong in a row. The incumbent champion, Steve Bahnaman, prevailed over Holzhauer, who did not receive any winnings.

While aggressive betting is disadvantageous if a player responds incorrectly, Holzhauer was correct on 72 of the 76 Daily Doubles he hit (94.7%). This strategy was not entirely new; Alex Jacob, also a professional gambler, used a similar strategy in his six regular-play wins in April 2015 as well as the 2015 Tournament of Champions, which he won.

Holzhauer was defeated in his 33rd game, which aired on June 3, 2019, and was watched by 14.5 million people. The winner, Emma Boettcher, used many of the same strategies Holzhauer used during his run.

In July 2019, Jeopardy! confirmed that Holzhauer would return for the Tournament of Champions in November. Holzhauer won both his quarterfinal and semifinal games to advance to the final round, which featured a rematch against Boettcher, who was invited separately and also won her first two tournament games. Holzhauer won the two-day final, winning the first game by a larger margin than Boettcher won the second and claiming the $250,000 top prize.

Holzhauer debuted at the World Series of Poker in 2019. In his first event, he finished 454th out of approximately 1,800 contestants and did not win any prize money (he would have needed to finish at 281st or higher to win any prize money). His second event was a tag-team match in which he partnered with Mike Sexton. He ultimately was knocked out as a solo contestant in round 17 of the tournament, with his most notable prize win being a $600 profit for finishing 92nd out of 1,867 on a No-Limit Hold’em Super Turbo Bounty game.

Holzhauer said he intended to donate some of his Jeopardy! winnings to Las Vegas children’s charities. On April 7, 2019, he donated $10,000 to a Las Vegas organization for displaced teens. On May 2, 2019, he was awarded a key to the Las Vegas Strip for his success on Jeopardy! and for his donations to children’s charity organizations and other nonprofit organizations in the Las Vegas area. In mid-2019, Holzhauer donated $1,109.14 (representing his daughter’s birthday) to the 2019 Naperville Pancreatic Cancer Reach Walk in Illinois, in Alex Trebek’s name. On June 24, 2019, Holzhauer began participating in World Series of Poker events in Las Vegas. He plans to donate half his winnings to the Las Vegas nonprofit Project 150, which helps homeless, displaced and disadvantaged high school students.

Bob Boden, the producer of The Chase, was impressed by his performance and had Holzhauer audition to join the show as a colleague of Labbett. In July 2020, Holzhauer and several other famous game show contestants were said to be in negotiations to become chasers for a potential reboot of The Chase, which would be produced for ABC.

The following week, Jeopardy! announced that Holzhauer would compete against Jennings and Rutter in prime-time specials for a million-dollar prize in Jeopardy! The Greatest of All Time, which aired in January 2020. Holzhauer won one match in the tournament, but lost to Jennings in the other matches, and received the runner-up prize of $250,000.

Holzhauer is a lifelong fan of the Chicago Cubs; he has said his dream job is a front-office position with the team and has actively sought employment in Major League Baseball. Holzhauer has said that he was contractually obligated to a non-compete clause in an agreement with the Jeopardy! producers; it expired in January 2020.