DeChambeau made his PGA Tour debut as an amateur in June 2015 at the FedEx St. Jude Classic near Memphis, Tennessee, and finished in 45th place. He played in his first major championship at the U.S. Open at Chambers Bay, but missed the cut by four strokes. DeChambeau was unable to defend his NCAA title in 2016 after the SMU athletic department was handed a postseason ban by the NCAA. He decided to forgo his senior season to play in a number of events before turning professional. At the 2015 Australian Masters in November, DeChambeau was runner-up with John Senden and Andrew Evans, two shots behind the winner Peter Senior. He was the low amateur at the Masters in 2016 and tied for 21st place.
U.S. Open: Established the first-round lead at the U.S. Open with a 7-under 65 and was in the mix all week at Erin Hills. Followed with 73 to be one back through 36 holes. Third-round 68 had him two adrift headed into final round. Closed with even-par 72 to finish six back of Brooks Koepka at T5. In nine U.S. Open appearances, has advanced to the weekend five times and never broken par in the final round.
On 28 January 2010, Lowry agreed a deal which would take him on a loan to Leeds United until 13 March 2010, joining his fellow Australian international teammates Patrick Kisnorbo and Neil Kilkenny. He made his debut for Leeds against Colchester United, playing left back for Leeds. After an impressive debut, Lowry suffered a minor injury and had to be substituted and replaced by Bradley Johnson after 70 minutes. After missing the FA Cup replay against Tottenham Hotspur due to not being eligible, Lowry returned to the Leeds starting lineup in the following game against Hartlepool United.
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.
Though he appeared in two matches as an un-used substitute for Aston Villa in the 2010–11 season, Lowry continued to be remain out of the first team and in January 2011, Lowry signed for Championship side Sheffield United until the end of the season making his first start for the Blades away at Coventry City a day later. Lowry made eighteen appearances for the Blades but with the club in decline he was unable to prevent them from being relegated at the end of the season.
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.
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).
U.S. Open: Playing alongside eventual-champion Martin Kaymer in the final pairing Sunday, followed up his career-best round (3-under 67) in a U.S. Open with a final-round, 2-over 72 to remain T2 (the sixth runner-up finish of his career). It was his best performance in six U.S. Open starts (previous-best finish was a T10 in 2013). It was also his top major championship showing among his 18 starts (previous-best finishes were T5s at the 2011 Open Championship and the 2014 Masters). His pairing with the 29-year-old Kaymer was just the third final grouping at the U.S. Open since 1965 with two players in their 20s. The others were John Mahaffey (28) and Jerry Pate (22) in 1976 and Woods (26) and Sergio Garcia (22) in 2002.
Lowry received his first call-up to the full Australia squad for a friendly against the Netherlands in Sydney and the Asian Cup qualifier against Oman in Melbourne in October. He did not play in either match. On 11 May 2010 he was selected as part of Pim Verbeek's 30-man provisional squad for the 2010 World Cup, and travelled to South Africa, but was not included in the final 23-man World Cup squad. Lowry was named in Han Berger's 18-man squad for an August 2010 friendly against Slovenia, but he did not appear in the match.
On 27 January 2016, Lowry returned to Australia after a decade away from Australia when he signed a two-and-a-half-year deal with A-League side Perth Glory. Upon joining Perth Glory, Lowry said of the move, quoting: "I've got a lot of experience behind me now and I want to use it to guide the young lads who are in this young squad. I've spent 11 years in England and it's shaped my football over there and I'm really happy to be here and get stuck into the games"