Lowry elected to turn professional the week after his Irish Open triumph, meaning that he would miss out on the opportunity to play in the Walker Cup in September 2009. He made his professional début on 28 May at the European Open, where he shot 78 in the first round to end the opening day almost at the back of the field, and went on to miss the cut following a second round 73.
the Memorial Tournament presented by Nationwide: Erased a five-stroke deficit in the final round and briefly held the lead before eventually shooting a final-round 70 to finish runner-up in the Memorial Tournament, three shots behind Jason Dufner. Hit a 350-yard drive on the 72nd hole and had just 136 yards to the pin when play was called for inclement weather for the second time during the final round. When play restarted, he made a costly bogey at the last to fall into a tie for second. Ranked No. 1 in fairways hit for the week with 45 of 56. Was also 8 of 11 in sand saves to rank first for the week.
Quicken Loans National: Starting the final round of the Quicken Loans National seven shots back, the Quicken Loans ambassador recorded a career-best nine birdies to post his low round of the week, a 5-under 65 to finish T3. Marked his third top-five in his last four starts. Chances for victory took a serious hit with a double bogey (the only one of the final round) on No. 14, the easiest hole in the final round. Marked second top-three finish in six starts at the Quicken Loans National (2015-2nd).
Lowry made his debut for the Glory on 30 January 2016, starting against Melbourne Victory. Lowry then scored his first Perth Glory goal on 20 February 2016 when he scored a header in the 41st minutes, to give Brisbane Roar a thrashing with a 6–3 win for Perth Glory. Throughout the 2015–16 season, Lowry established himself in the starting eleven and formed a central defense partnership with Alex Grant, as he made ten appearance for Perth Glory in his first half of the season.
Kolon Korea Open: Won his first tournament as a professional, the Kolon Korea Open on the OneAsia Tour, when he rolled to a six-stroke win over Rory McIlroy at Woo Jeong Hills CC in early October. He took control of the tournament in the third round when he shot an 8-under 63. He followed that with a 3-under 68 Sunday. The victory was worth a little under $250,000.
Deutsche Bank Championship: Shot a final-round 3-under 68 to come from one shot back and defeat third-round leader Henrik Stenson at the Deutsche Bank Championship, good for his third career PGA TOUR victory. Earned the win at age 26 years, 8 months, 25 days in his 150th career start. Collected 2,000 points and moved from No. 22 to No. 3 in the FedExCup standings. Has come from behind to win all three of his PGA TOUR events, with his first two wins via playoffs (2012 Wells Fargo Championship and 2015 PLAYERS Championship). Became the sixth consecutive come-from-behind winner at TPC Boston.
On July 16, 2017, DeChambeau earned his first PGA Tour victory by winning the John Deere Classic by a single stroke over Patrick Rodgers. He carded a round of 65 in the final round to win his maiden title in his 40th start on tour. The win coming the week before, gained DeChambeau a place in the 2017 Open Championship, where he missed the cut after rounds of 76–77 (+13).