On 23 November 2011, Lowry was again loaned out to play in the Championship, this time to Millwall until 3 January 2012. He followed Aston Villa team-mate Nathan Baker who also signed on loan for Millwall two days earlier. Lowry made his Millwall debut three days later, where he played 90 minutes, in a 0–0 draw against Crystal Palace. His impressive display at Millwall soon earned a loan extension. Weeks later on 13 January 2012, Lowry was sent-off in the 22nd minutes after stamping on Nikola Žigić, which saw Millwall lose 6–0. Three years on after signing for Birmingham City, Lowry stated, quoting: "Whatever club I play for I fully commit to that club at the time. I play with my heart on my sleeve. Sometimes in the past I have gone overboard but I was a younger player then, I have learned a lot from these types of experiences. But I am an aggressive player, that’s the way I like to play and I can’t change the way I play. I will use my experience now and be a bit more clever."'
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).
At the 2016 U.S. Open at Oakmont Country Club near Pittsburgh, Lowry shot 65 (−5) in the third round for 203 (−7) and a four-stroke advantage over Dustin Johnson and Andrew Landry at the 54-hole stage. The 65 was Lowry's joint career best round at a major championship. Due to weather delays on Thursday, the third round was not completed until early on Sunday, and Lowry birdied two of his remaining four holes to extend his two stroke overnight lead to four. In the final round he was in contention for the title, within one shot of Dustin Johnson after 12 holes, before three consecutive bogeys on holes 14, 15 and 16 ended his chances. He finished the tournament tied for second place, with a final round score of 76.
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.