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.
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.
Born in Modesto, California, to John Howard Aldrich DeChambeau and Janet Louise Druffel, DeChambeau moved to Clovis, east of Fresno, at age seven. He attended Clovis East High School and won the California State Junior Championship at age 16 in 2010. DeChambeau graduated in 2012 and accepted a scholarship to Southern Methodist University in Dallas, Texas, majoring in physics.
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.
On 23 November 2011, Lowry was again loaned out to play in the Championship, this time to Millwall until 3 January 2012. He followed Aston Villa team-mate Nathan Baker who also signed on loan for Millwall two days earlier. Lowry made his Millwall debut three days later, where he played 90 minutes, in a 0–0 draw against Crystal Palace. His impressive display at Millwall soon earned a loan extension. Weeks later on 13 January 2012, Lowry was sent-off in the 22nd minutes after stamping on Nikola Žigić, which saw Millwall lose 6–0. Three years on after signing for Birmingham City, Lowry stated, quoting: "Whatever club I play for I fully commit to that club at the time. I play with my heart on my sleeve. Sometimes in the past I have gone overboard but I was a younger player then, I have learned a lot from these types of experiences. But I am an aggressive player, that’s the way I like to play and I can’t change the way I play. I will use my experience now and be a bit more clever."'
Lowry started the 2018-19 season with partial status after finishing 140th in the FedEx Cup. He moved into a share of the 36-hole lead at the 2019 Open Championship at Royal Portrush, after successive opening rounds of 67. He was tied at eight under with J. B. Holmes. Lowry then shot a 63 for a new course record to lead by four strokes at the end of the third round. He won the tournament by six shots ahead of Tommy Fleetwood.
In the 2013–14 season, Lowry suffered a minor thigh strain in the club's pre-season friendly. Despite this, Lowry remained in the first team under the new management of Steve Lomas until he received a straight red card after a foul on Will Hughes, in a 5–1 loss against Derby County on 14 September 2013. After serving a three match ban, Lowry remained on the bench without playing for four matches Lowry made his first team return on 2 November 2013 when he came on as a substitute for Scott Malone against Burnley. However, his return, after spending two months without playing, was a disastrous when he scored an own goal, which saw Millwall drew 2–2. After this, Lowry was out of the first team, demoted to the substitute bench between mid-November and mid-December until he made his return on 26 December 2013, in a 4–0 loss against Watford. On 28 January 2014, Lowry was sent-off for the second time this season in the late-minutes against Sheffield Wednesday after fighting with Giles Coke, who also was sent-off as well, with both side drew 1–1. After serving a four match ban, Lowry was in the first team throughout February and March until he suffered a foot injury that kept him out for the remainder of the season. Lowry went on to finish the 2013–14 season, making twenty-two appearance.
Lowry made his professional debut in the 2009–10 UEFA Europa League in an away fixture at Rapid Vienna. On 17 September 2009, Lowry signed a three-month loan deal with Football League Championship side Plymouth Argyle. Lowry made his Plymouth Argyle debut on 19 September 2009, playing 90 minutes, in a 3–1 loss against Newcastle United. He played 13 league games for Plymouth during his loan spell, where he impressed many and was recalled by Villa who required Lowry's services as cover after some injuries to defenders.
Waste Management Phoenix Open: Claimed his second runner-up finish at the Waste Management Phoenix Open, one shot behind Hunter Mahan. Had birdie opportunities on the last three holes but unable to catch Mahan. Previously lost in a playoff to Troy Matteson just down the road at Grayhawk GC in the 2009 Frys.com Open. Had he won at TPC Scottsdale, would have become the first Sponsor Exemption to do so since Jason Gore (2005 84 Lumber Classic). Lee Westwood later won in June as a Sponsor Exemption at the St. Jude Classic presented by Smith & Nephew.
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.