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.
In the 2012–13 season, Lowry regained his first team place, playing in the left-back and central defense positions until he missed one game after picking up a yellow card for the fifth time against Bristol City on 2 October 2012. After making his first team return as a left-back, Lowry then provided assist for the winning goal when he set up a goal for Chris Woods, in a 1–0 win against his former club, Leeds United on 18 November 2012. Lowry was then banned for two matches between 19 January 2013 and 25 January 2013 after picking up a yellow card for the tenth time this season. Lowry then He "curled a superb, dipping free-kick" to score from 35 yards (32 m) as Millwall beat Charlton Athletic 2–0 at The Valley on 16 March 2013. Lowry played in all matches in the run up to the Lions' FA Cup semi final against Wigan Athletic at Wembley, though he missed one match in the 4th round against his former club, Aston Villa. In late-April, Lowry was given a three match ban after being booked for the fifteenth time this season. Despite this, Lowry finished the 2012–13 season, making forty-five appearance and scoring once in all competitions.
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.
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).
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.