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.
Wells Fargo Championship: Made birdie-3 on the first extra hole (No. 18) to defeat Rory McIlroy and D.A. Points at the Wells Fargo Championship for his first TOUR win. Improved to 1-1 in playoffs (lost to Troy Matteson, 2009 Frys.com Open). The playoff was the fifth at the Wells Fargo Championship. At the age of 23 years, 4 months, 23 days, became the third player to make the Wells Fargo Championship his first PGA TOUR win (Anthony Kim in 2008 and McIlroy in 2010). Became the third-youngest winner of the event, behind McIlroy (20 years, 11 months, 28 days) and Kim (22, 10, 15). His win came in his 72nd start on TOUR and was his 16th top-10 finish. Opening-round 66 is the lowest start by a winner of the Wells Fargo Championship. Won in his third start at the Wells Fargo Championship (T6 in 2010 and T16 in 2011).
In 2008, Fowler repeated as Sunnehanna Amateur champion. In the first round of the U.S. Open, Fowler shot a −1 (70) and was in a tie for 7th place. He was one of three amateurs to make the cut, along with Derek Fathauer and Michael Thompson. He ended the tournament tied for 60th. In October 2008 Fowler played on the Eisenhower Trophy team that finished second. He was the leading individual player.
OHL Classic at Mayakoba: Birdied two of his last three holes at the OHL Classic at Mayakoba to fire a final-round 67 and finish in 2nd place, one shot back of Patton Kizzire. In his first start at the event, opened with a bogey-free, 6-under 65 to sit three back of Kizzire's lead. Followed with three-consecutives rounds of 67 in rounds two through four, resulting in a score of 18-under 266. Due to inclement weather Saturday, played his final two rounds on Sunday.
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.