Immediately after the Masters in mid-April 2016, DeChambeau turned professional and signed a long-term agreement with Cobra-Puma Golf. He made his pro debut days later at the RBC Heritage in South Carolina and tied for fourth, earning over $259,000. The decision to turn professional meant the forfeiture of his exemptions to the U.S. Open at Oakmont and Open Championship at Royal Troon; he qualified his way into the U.S. Open, tied for fifteenth place for over $152,000, and improved his world ranking to 148.
Lowry did not win on the European Tour from 2016 to 2018 but was joint runner-up in the 2017 DP World Tour Championship, Dubai and runner-up in the 2018 Andalucía Valderrama Masters. In January 2019 he won the Abu Dhabi HSBC Championship by a stroke from Richard Sterne. Lowry led by 3 strokes after three rounds but was two-over-par after 11 holes of his final round and dropped 4 shots behind Sterne. However he finished with 3 birdies in the final 7 holes, while Sterne had two bogeys, giving Lowry the victory.
World Golf Championships-HSBC Champions: Came to the 72nd hole in need of a birdie to get into a playoff with Tim Clark and Bubba Watson at the World Golf Championships-HSBC Champions. Hit a 5-wood from the fairway that came up short and went in the water on the par-5. Made par after taking a penalty and finished T3 after a final-round 70 at Sheshan International GC in Shanghai.
PGA Championship: With his T5 finish at the PGA Championship, finishing three strokes behind champion Justin Thomas, continued to be a top-five machine in major championships, recording his seventh such finish in 32 starts. Made a furious Sunday rally, with six birdies, including four in a row on Nos 12-15, but pars on The Green Mile (Nos. 16-18) left him a few short of his friend, Justin Thomas.
The Honda Classic: After beginning the final round of The Honda Classic with a four-stroke lead, posted a 1-over 71 to win by the same margin for his fourth career PGA TOUR title. It marked the first of five 54-hole leads he converted to victory. Opened with back-to-back 66s for the second consecutive year and posted a 65 in the third round to post the best 54-hole total since the event moved to PGA National in 2007 at 13-under 197. Seized the 54-hole lead with the widest margin of his career entering a final round. Turned in 2-over 37, but posted three birdies on the back nine to take command of the tournament. Despite bogeys on the 71st and 72nd holes, claimed his first victory since the 2015 Dell Technologies Championship. Finished the week second in Strokes Gained: Putting (7.392) and moved to 10th in the FedExCup standings and ninth in the Official World Golf Ranking, his first time in the top 10 since the 2016 BMW Championship.
On June 3, 2018, DeChambeau won the Memorial Tournament in Dublin, Ohio, in a sudden-death playoff against Kyle Stanley and An Byeong-hun, after the three finished regulation play tied at −15. After Stanley bogeyed the first hole of sudden death, DeChambeau then proceeded to win with a birdie on the second hole, giving him his second win on the tour.