The defeat would have brought back bad memories for The Ospreys whose last league defeat came at the same ground in December last year.
The Munstermen have now won four in a row against their Welsh rivals, a double in last season’s European Cup plus the 13-9 win in Cork last season.
Leading the tryfest for the Irish province were man of the match Anthony Horgan (two), John Kelly and Shaun Payne shared four tries at Musgrave Park.
Ospreys fly-half Matthew Jones kicked his side into a fifth-minute lead but his effort was soon cancelled out by Munster’s Paul Burke.
Paul Burke landed the leveller six minutes later before Munster fizzed some fast-paced attacking into their play.
The hosts began to take control of the game and soon had the first try of the game.
On 22 minutes, some good work from scrum-half Peter Stringer, Burke and Trevor Halstead saw Horgan go over in the corner.
Burke added the extras and Munster soon stretched their lead, aided by some poor defence by The Ospreys.
Horgan again was the benefactor as he beat the flat-footed Stefan Terblanche to put Munster ahead 17-3.
There was further woe for the visitors when Horgan once again caused chaos in their defence before putting Kelly in for another try.
The conversion from Burke ensured they went into the break 27-3 ahead.
Another Burke penalty followed after the break and then then the Opsreys suffered a further blow with a suspected broken knee cap for centre David Bishop.
Declan Kidney’s charges closed out game with a final try for Payne.
Manning converted and although Ospreys captain Barry Williams grabbed a converted try in injury time, there was little to stop Munster from joining Edinburgh at the top of the table.