On the eve of his appearance before a disciplinary hearing in Glasgow, on charges of violent conduct, Gavin Henson looked badly out of sorts, tentative in attack and defence.
Deiniol Jones, Chris Czekaj and Craig Morgan all claimed tries for the visitors, with Nick Robinson grabbing 13 points with the boot.
It was the Blues' first victory on the road against a fellow Welsh side since regions were introduced in 2003.
The Osprey's points came from three penalties, two by Shaun Connor and one from Kiwi Adrian Cashmore.
The Blues turned around with a 14-6 advantage after repeatedly punching holes in the Ospreys defence.
Jones went over for the first score on seven minutes after Mike Phillips, Morgan, Robin Sowden-Taylor and Rhys Williams had opened the home rearguard.
Then Jamie Robinson picked a perfect line and sent out a flighted pass for wing Czekaj to dash across.
The Ospreys struggled to cope with Cardiff's superior commitment and pace all night, and the defeat could have been worse.
|Ospreys Score Card|
|Cardiff Blues Score Card|