Lowry received his first call-up to the full Australia squad for a friendly against the Netherlands in Sydney and the Asian Cup qualifier against Oman in Melbourne in October. He did not play in either match. On 11 May 2010 he was selected as part of Pim Verbeek's 30-man provisional squad for the 2010 World Cup, and travelled to South Africa, but was not included in the final 23-man World Cup squad. Lowry was named in Han Berger's 18-man squad for an August 2010 friendly against Slovenia, but he did not appear in the match.
PGA Championship: Finished T3 and two strokes behind McIlroy at the PGA Championship in his 20th major championship start, with T19 in 2013 the previous-best finish in four prior PGA Championship starts. Became the first to claim top-five finishes in all four majors since Woods in 2005. Since 1934, is just the third player to perform the feat, joining Woods in 2000 and 2005 and Jack Nicklaus in 1971 and 1973. Played all four majors in 32-under, with McIlroy second on the list, at 27-under.
The Open Championship: Playing in the final group Sunday for the second straight time in a major championship, made a solid bid for the title, at The Open Championship, with a final-round, 5-under 67. Along with Garcia, finished second to Rory McIlroy by two strokes. With his finish at Royal Liverpool GC, became the only player of the season to claim top-five finishes in the year's first three major championships. He also became the first player to claim top-10 finishes in a season's first three majors since Woods achieved the feat in 2005. His T2 at Royal Liverpool supplanted his previous-best Open Championship finish (in four starts) of T5 in 2011. Rounds of 69-69-68-67 made him the only player in the field to post all four rounds in the 60s.
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."'
U.S. Open: Playing alongside eventual-champion Martin Kaymer in the final pairing Sunday, followed up his career-best round (3-under 67) in a U.S. Open with a final-round, 2-over 72 to remain T2 (the sixth runner-up finish of his career). It was his best performance in six U.S. Open starts (previous-best finish was a T10 in 2013). It was also his top major championship showing among his 18 starts (previous-best finishes were T5s at the 2011 Open Championship and the 2014 Masters). His pairing with the 29-year-old Kaymer was just the third final grouping at the U.S. Open since 1965 with two players in their 20s. The others were John Mahaffey (28) and Jerry Pate (22) in 1976 and Woods (26) and Sergio Garcia (22) in 2002.
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 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.