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 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.
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.
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.
The form and fitness of centre-backs Michael Morrison and Jonathan Spector and left-back Jonathan Grounds restricted Lowry to a seat on the bench until mid-December. He eventually made his debut in the starting eleven for the home fixture against Cardiff City on 18 December, standing in for the injured Grounds at left back. He appeared once more, in the FA Cup, before his contract was cancelled by mutual consent to enable him to return to Australia.
Enjoyed a stellar rookie season, with seven top-10 finishes and a 32nd-place finish in the FedExCup standings that led to him winning PGA TOUR Rookie of the Year honors. Finished inside the top 30 on the money list to qualify for the Masters and the U.S. Open. Played in first three Playoff events, slipping from 21st to 32nd and out of the TOUR Championship.
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.
World Golf Championships-Accenture Match Play Championship: In his fourth consecutive start at the World Golf Championships-Accenture Match Play Championship, fought his way to the semifinals Sunday morning against Ernie Els. Got off to a hot start, leading for seven of the first nine holes. With a shift of momentum, Els battled back and won three consecutive holes (Nos. 10-12) to gain a 2-up lead. Following an eagle and par on Nos. 13 and 14, he squared up the match. An Els birdie-3 at No. 18 sent the match to extra holes. A birdie-3 at the 19th hole (No. 1) gave him the upset win over Els.
Hero World Challenge: After beginning the final round seven strokes out of the lead, closed with a tournament-record, personal-best 11-under 61 to win the Hero World Challenge by four strokes over Charley Hoffman. With a winning score of 18-under 270, won at the age of 28 years, 11 months and 20 days. His 61 topped the previous Hero World Challenge course record of 62, set by Albany resident Justin Rose during the final round in 2015. Prior to his 61, the previous low final-round score by a Hero World Challenge winner was 64, set on three occasions and most recently by Luke Donald in 2005. Opened his final round with seven birdies before making his first par on the par-4 eighth hole. No player has had as long a streak of birdies in an official PGA TOUR event to open a round since Joe Durant started round four of the 2005 Honda Classic with seven in a row. Added a birdie on the ninth hole to make the turn with an 8-under 28, turning a seven-stroke deficit into a two-stroke lead. His final round included 11 birdies, two more than his benchmark of nine birdies in official PGA TOUR events (final round of the Quicken Loans National in 2017). Finished the week at Albany Golf Club with 30 birdies, three more than his highest total in official PGA TOUR events (27 – 2017 Houston Open). Recorded his sixth top-six finish at the event in his sixth start (1/2017, T3/2016, 3/2015, T6/2014, T4/2012, T6/2011).
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.
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.