The Irish side repeated their shock 2008 final victory over the most successful team in the competition's history thanks to tries by Keith Earls, Dave Kilcoyne, CJ Stander, Casey Laulala, Simon Zebo and Paul O'Connell.
Toulouse, four-times Heineken Cup winners, trailed 27-9 ten minutes after halftime but a fine try by winger Hosea Gear gave them hope before Munster eased away in the final quarter with scores by Laulala, Zebo and O'Connell.
Munster started fast and winger Earls crossed in the right corner for the opening try after five minutes.
The hosts continued to batter Toulouse and two penalties by flyhalf Ian Keatley stretched the lead to 13-3 after Luke McAlister had kicked the French side's first points.
Munster suffered a huge blow when their captain Peter O'Mahony limped off injured and McAlister cut the halftime deficit to 13-9 with two penalties.
The hosts began the second half as explosively as they did the first and rocked Toulouse with two quick tries.
Prop Kilcoyne burrowed over from close range and replacement Stander also capitalised on the dominance of the Munster forwards, led by Ireland lock O'Connell, to cross the line.
New Zealander Gear conjured up an excellent long-range try as the mercurial French side briefly flickered into life but Munster regrouped and Keatley's penalty stretched the lead before Laulala powered over in the left corner.
Joe Tekori surged over the Munster line for a consolation try for the visitors but Zebo and O'Connell crossed for rampant Munster in the dying minutes to seal a famous victory.
Clermont Auvergne host Leicester and Saracens visit Ulster later on Saturday. Holders Toulon entertain Leinster on Sunday.
- Sports & Recreation
- Simon Zebo
- Casey Laulala
- Dave Kilcoyne
- Keith Earls