In February 2010, Fowler finished second at the Waste Management Phoenix Open with a score of 15-under-par at the TPC of Scottsdale course. In June, Fowler notched his third PGA Tour runner-up finish at the Memorial Tournament in Dublin, Ohio. Fowler entered the final round in the lead, but shot a 73 to finish behind Justin Rose, who recorded his first PGA Tour victory. This performance took Fowler into the top 50 of the Official World Golf Ranking.
Waste Management Phoenix Open: Two weeks after the win in Abu Dhabi, made his eighth consecutive start in the Waste Management Phoenix Open, where he found himself three strokes off the lead after 54 holes. A final-round 4-under 67, capped off by a clutch birdie on the 72nd hole, forced sudden death with Hideki Matsuyama. On the fourth extra hole, the par-4 17th, an errant tee shot found the water hazard for the second time of the day. Matsuyama made par to win. Ranked second in Strokes Gained: Tee To Green and T1 in Strokes Gained: Total at TPC Scottsdale.
Lowry made his Leyton Orient debut, playing as a left-back position, in the opening game of the season, which saw Leyton Orient lost 2–1 to Chesterfield. Since his debut, Lowry established himself in the left-back position in the first half of the season despite being sidelined with suspension and fitness concern that saw him out for two matches. Following his return to the first team, Lowry played in the central-defense between December and March until he dropped from the first team throughout March. Lowry went on to make his first team return throughout 2014–15 season, making thirty-four appearance in his first season at Leyton Orient.
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.
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.
Frys.com Open: At the Frys.com Open in Scottsdale, Ariz., reached a three-way playoff with Jamie Lovemark and eventual-winner Troy Matteson. Began the final round four strokes behind Matteson, but played his first five holes in 5-under, punctuated by a hole-in-one from 211 yards at the par-3 fifth hole. After finishing T2 in the playoff, he had recorded all eight of his professional rounds in the 60s. Thanks to the T7 in Las Vegas at the Justin Timberlake Shriners Hospitals for Children Open and T2 finish at Grayhawk GC, he surpassed No. 150 from the 2008 money list, earning special temporary membership on TOUR for the remainder of the season.
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.
BMW Championship: Entered the BMW Championship No. 36 in the FedExCup standings, with his T39 finish at Conway Farms outside Chicago leading to a final ranking of No. 38. Advanced to the TOUR Championship by Coca-Cola in 2012 (finished No. 28 in the FedExCup), but other three seasons led to near misses of cracking the top 30 in the FedExCup (No. 43 in 2011 and No. 32 in 2010).
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.