[6] It was with Booth that Lee won the WBO belt in 2014, becoming the first Irish boxer to win a world title on American soil since 1934.

Lee represented Ireland at the 2002 World Junior championships in Santiago de Cuba, competing in the middleweight category.

Lee fought five times in a week beating Ismail Sillakh and United States favourite Jesus Gonzales but lost the final to Cuban boxer Noelvis Diaz to claim the silver medal.

[4][5] At the World Amateur Championships in Bangkok, Lee was beaten on points by eventual winner Gennady Golovkin who also defeated Lucian Bute and Matt Korobov on his way to the gold medal.

"[9] His first professional bout was in March 2006, at the Joe Louis Arena, Detroit, in which Lee beat Anthony Cannon on a points decision over six rounds on a card that featured Johnathon Banks.

On 15 December 2007, Lee became the Irish Super-middleweight champion after he beat fellow Irishman Jason McKay at the National Stadium in Dublin.

Star coach Steward was also quick to praise Lee, claiming on RTÉ television that by the end of 2008 he would defeat the then current world champion, Kelly Pavlik.

The stoppage was mildly controversial, as Lee was winning on points, and was still punching back as the referee Tony Chiarantano stepped in.

On 21 March 2009, appearing on the undercard of the Bernard Dunne world title fight against Ricardo Cordoba, Lee beat the tough German brawler Alexander Sipos in a unanimous decision.

On 20 June 2009, Lee outpointed Olegs Fedotovs in front of 60,000+ at the Veltins Arena in Gelsenkirchen, Germany for his 18th victory as part of the Klitschko-Chagaev undercard.

On 22 August 2009, Lee stopped Andy Shuler in the 8th round of a bout in Hammond, Indiana to earn his 19th victory and 14th KO.

A hometown crowd turned out in Limerick, 14 November 2009, to watch Lee defeat Frenchman Affif Belghecham in a ten-round battle of the southpaws.

On 12 March 2011, Lee fought Craig McEwan at Foxwoods Resort Casino in Mashantucket, Connecticut, and won via technical knockout at 0:56 in the 10th round.

Under the tutelage of new trainer Adam Booth, Lee returned to winning ways, after his loss to Chavez Jr., by outpointing former Irish super middleweight champion Anthony "The Pride" Fitzgerald (13–3, 4 KO's) over ten rounds in a middleweight fight held at the Odyssey Arena in Belfast on 9 February 2013 on the undercard of a Carl Frampton Vs Kiko Martinez EBU (European) super bantamweight title fight.

[13] On 7 June 2014, in Madison Square Garden, on the undercard of the Pay-Per-View fight between Miguel Cotto and Sergio Martinez, Andy Lee met hard-hitting Virgin Islander John Jackson in a 154-lb bout.

Lee regained his composure but proceeded to lose the next 3 rounds in a row, he spent the majority of the time tactically looking to catch Jackson coming in with a right hook counter.

After the comeback knockout victory over John Jackson, Andy Lee secured himself a 13 December WBO World Middleweight Title shot against the then undefeated former 2008 Russian Olympian, Matt Korobov, on the HBO triple-header that featured the fight between Timothy Bradley and Diego Chaves as its main event.

However Korobov regained control and seemed to be controlling the pace of the fight until round 6, when Lee connected on a right hook in an exchange and badly hurt Korobov, a flurry of 18 straight unanswered punches forced referee Kenny Bayless to stop the contest handing Lee the 6th-round TKO victory and the WBO World Middleweight Title.

Quillin failed to make weight at the weigh-in for the bout however, meaning regardless of the result of the fight, he was ineligible to win Lee's WBO Middleweight World Title.

It was announced that on 19 September 2015, Andy Lee would defend his WBO Middleweight title against unbeaten Billy Joe Saunders in his home city of Limerick, Ireland.