Turned professional in 2016 after an eye-catching performance at the Masters Tournament, when he finished in a share of 21st as the defending U.S Amateur Champion. He then claimed a top 15 finish at that year's U.S. Open.

Did not qualify for the a PGA TOUR card after the then-Web.com Tour’s regular season in 2016, but eventually earned his card after winning the DAP Championship during the Web.com Tour Finals.

Won his first PGA TOUR title in 2017 at the John Deere Classic. Enjoyed a breakout year in 2018 as he won the Memorial Tournament and two FedEx Cup Play-Off events at The Northern Trust and Dell Technologies Championship. Earned a debut appearance for the United States at The Ryder Cup at Le Golf National as one of Jim Furyk’s Captain’s Picks and won his fourth title of the calendar year at the Shriners Hospitals for Children Open.

Lifted his first DP World Tour trophy in 2019 with a commanding seven shot victory at the Omega Dubai Desert Classic, where he set a new tournament record score with a 24 under par total.

Underwent a major physical transformation in preparation for the 2020 season, which yielded a sixth PGA TOUR title at the Rocket Mortgage Classic and a maiden Major Championship at the U.S. Open at Winged Foot. DeChambeau was the only player under par as he romped to a six-stroke victory.

Held off the unlikely challenge of a resurgent Lee Westwood to win the 2021 Arnold Palmer Invitational, carding a one under par final round to win by one stroke at Bay Hill and later that year made his second Ryder Cup appearance, earning two and a half points from three matches as the United States won at Whistling Straits.

Claimed his second Major Championship in 2024 at the U.S. Open at Pinehurst, finishing one stroke ahead of Rory McIlroy.

Represented the United States for a third time at the 2025 Ryder Cup, qualifying by virtue of his performances in Major Championships that season, recording three top tens including a runner-up finish at The 153rd Open.