The South African centre Jean de Villiers and former All Blacks winger Doug Howlett scored tries as Munster smashed Perpignan's proud five-year European Cup home winning record.
Munster, the 2006 and 2008 winners, beat the French champions 37-14, ending Perpignan's 16-match winning streak at their Stade Aime Giral stronghold.
The Irish province, whose other tries came from Denis Fogarty and Denis Hurley, top Pool One and stayed on course for the quarter-finals while Perpignan are eliminated.
It was the French team's first home loss in the tournament since 2004 when they were defeated by Wasps.
Angry French giants Stade Francais took out their European Cup frustrations with a revenge 29-16 victory over Ulster.
Stade were furious at the six-month ban handed out to scrum-half Julien Dupuy after the player was punished for eye-gouging Ulster flanker Stephen Ferris in the 23-12 loss in Belfast last week.
In Pool 2, where Biarritz are virtually assured of taking the group after four wins in four matches, Gloucester beat Glasgow 22-7 to move into second spot, 10 points behind the French side.
At a snowbound Edgeley Park, Sale came back from a 14-8 half-time deficit to beat Harlequins 21-17 and keep the pressure on Pool 5 leaders Toulouse who defeated Cardiff Blues on Saturday 23-7.
Tries from Nick Evans and Aston Croall put Quins in charge at the interval despite Sale No.8 Sisa Koyamailbole having given his side an early lead.
Sale prop Eifion Roberts then edged the Sharks back in front with Charlie Hodgson contributing 11 points with the boot.
