Wales scrum-half Rhys Webb made a successful return from injury as the Ospreys won 21-17 to become the first team to beat Munster in Cork since January 2013.
Munster had won 12 games on the bounce at Musgrave Park since a loss to Cardiff Blues over three years ago, but Owen Watkin's first regional try and 16 points from man-of-the-match Sam Davies guided the Ospreys to a hard-earned PRO12 victory.
Three tries were scored in an entertaining and evenly-balanced first half, Duncan Williams' charge-down effort for Munster and a tremendous first score in red by Francis Saili sandwiching Davies' 24th-minute touchdown.
A Davies penalty cut the gap to 12-10 by half-time and while Munster replacement Robin Copeland went over to put seven points between the sides, Webb's introduction for his first appearance in five months, coupled with Watkin's touchdown and two more Davies penalties, saw Steve Tandy's men finish on top.
There was little action of note until Williams blocked his opposite number Brendon Leonard's attempted box-kick and gathered to run in a fine 40-metre try in the 11th minute.
Ian Keatley's conversion was followed by further Munster pressure, but it was his pass that almost led to a long-range intercept try from Tom Grabham. Darren Sweetnam prevented the score with an excellent tackle on his 22-metre line.
However, a multi-phase attack, sparked by impressive distribution from half-backs Leonard and Davies, had the Ospreys level by the 25-minute mark. Joe Bearman and Josh Matavesi carried strongly before Davies spotted a gap to touch down wide on the right.
Davies curled over a peach of a conversion but it was his midfield fumble that handed Munster possession for their second try. Dave Kilcoyne got over the gain-line and Saili sliced through over the 10-metre line, showing great feet to glide past Ben John on the outside and make the right corner.
Keatley's conversion hit the near post and the Ospreys almost manufactured a quick response, their South African centre JJ Engelbrecht threatening on a kick chase that was covered by Sweetnam.
Davies grabbed the final points of the half with a 37th-minute penalty and with heavy rain making for a defence-dominated third quarter, it took a sublime offload from the fast-breaking Sweetnam to set up Copeland's five-pointer in the 50th minute.
Returning scrum-half Webb was then introduced, ending his five-month spell on the sidelines with a broken foot, and his half-back partner Davies clawed back three points after a Keatley offside.
Speedier service from Webb saw the Ospreys make sizeable inroads and although a Davies penalty attempt bounced back off the crossbar, the visitors swiftly built momentum again for Davies to send young replacement Watkin crashing wide on the left.
The difficult conversion proved beyond Davies, who was inches short of his second try in the 70th minute. It would have been a deserved score as the Ospreys' attack continued to click and Munster's misfired.
A collapsed maul allowed Davies to extend the lead to four points with three minutes and although Webb had to go off following an accidental clash of heads with Saili, the Ospreys knuckled down in defence to claim four valuable Guinness PRO12 points on the road.