He made his League of Ireland debut on 20 May 2005, keeping a clean sheet against Waterford, after the departure of Russell Payne. Having come through the club's youth system in 2004, where he was U21 Player of the Year, he made rapid progress to become the club's Young Player of the Year and Player of the Year for 2005. He played a total of 25 league games in his first season keeping seven clean sheets. Murphy kept 24 clean sheets from 35 games during the 2006 campaign as Rovers won the First Division. He made his 100th competitive appearance for The Hoops on 2 October 2007 at Bray Wanderers where for the first time in his Rovers career, he was not only booked but sent off. For the 2007 season he kept 16 clean sheets in 29 league games as Rovers finished fifth in the league. Midway through the 2009 season, Murphy was dropped as first choice goalkeeper by Michael O'Neill and replaced by new signing, Alan Mannus who held on to the position for the remainder of the campaign.
Having reportedly turned down a new contract at Shamrock Rovers, no press release confirming his departure was ever issued by the club, Murphy reportedly signed for rivals, Bohemians in time for the start of the 2010 League of Ireland season. It was confirmed on 6 February 2010 that Bohemians' transfer embargo had been lifted, and Barry Murphy was officially registered with the club. He was unveiled to the Bohemians fans in a pre-season friendly against Athlone Town, and made his league debut for Bohs at home to Sporting Fingal on 5 March. He made his European debut and kept a clean sheet when Bohemians beat The New Saints F.C. 1–0 in the 2010–11 UEFA Champions League qualifiers. However the following week Bohs were humiliated 4–0 in one of the worst results in the League's history. Murphy spent the first half of the season as first choice goalkeeper for Pat Fenlon's side but lost his place midway through the season after some poor performances. When Chris O'Connor was suspended towards the end of the season, Murphy regained his place and put in some man of the match performances, most notably against St. Patrick's Athletic on 9 October. Unfortunately for Murphy and Bohs, they would lose the league title on goal difference. This qualified them for the 2011–12 UEFA Europa League qualifiers where they played NK Olimpija Ljubljana. Murphy playing in both legs as Bohs were eliminated.
Murphy made his Ireland U23 debut in November 2007 and also kept a clean sheet in his second appearance. He then made his third appearance for the U23s in October 2008 against Belgium.
