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.
Lowry missed the first three cuts of his professional career, but had his first payday on 5 July, when he finished 50th at the Open de France ALSTOM. He had his best professional result in November 2009, when he finished 3rd in the Dunlop Phoenix Tournament in Japan. In January 2010, Lowry finished in fourth place in the Abu Dhabi Golf Championship, moving him into the top-100 of the Official World Golf Ranking.
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).
Aberdeen Asset Management Scottish Open: Earned his second international victory when he captured the Aberdeen Asset management Scottish Open in come-from-behind fashion at Gullane GC in July. After a bogey on the 14th hole Sunday, fell two shots off the lead. He responded with three birdies over his final four holes to catch and pass American Matt Kuchar, who shot a final-round 68 to post the clubhouse lead at 11-under. He made a 9-foot birdie putt at No. 15, made a two-putt birdie at the par-5 16th, parred the 17th then hit his approach shot on the par-4 finishing hole to 2 feet for the tap-in birdie and the title. Joined seven other players who made the Scottish Open their first European Tour win.
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"