Gareth Anscombe slotted over an early penalty for Cardiff Blues but Ospreys replied almost immediately through Sam Davies off the tee.
The Blues fell to a narrow 16-13 defeat to Leinster last weekend, having held a ten-point advantage at the interval but they seemed back to their best against the Ospreys as they dominated the early exchanges.
The Ospreys were penalised at the breakdown on the halfway line after 17 minutes, Anscombe found touch to bring his side back into the Ospreys 22m.
And a great driving maul from the resulting line-out saw Kristian Dacey drive over, with Anscombe adding the extras.
Ospreys were looking to return to winning ways following consecutive defeats to Leinster and Ulster in recent weeks, with Davies preferred to Dan Biggar at No.10 in an otherwise unchanged 15 from last weekend's loss at the Kingspan Stadium.
But the home side struggled to assert themselves against a pumped up Cardiff in the first quarter of the game.
Dan Fish's kick was charged down inside his own 22m by Davies on 20 minutes. Referee Nigel Owens looked to the TMO for a potential off the ball tackle and Fish was sin-binned attempting to atone for his error.
Ospreys kicked to the corner from the resulting penalty and Welsh international Alun Wyn Jones was the lucky recipient from the resulting pressure as he burrowed his way over for his 100th point for his side. Davies added the extras to level things up.
And it could have got worse for Cardiff on 24 minutes but Davies missed his drop goal to put the Ospreys in the box seat.
The Ospreys took further advantage of the extra man, as Eli Walker found space on the right to dive over on 27 minutes but Davies missed the conversion.
And things got even worse for Cardiff Blues minutes later as Walker scored his second try of the night for the now rampant Ospreys.
Dan Evans gathered a deep kick and broke to give the Ospreys a good platform, with the ball shipped wide to Walker to score and Davies added the extras to make it 22-10.
And the Ospreys sealed the bonus point, with Dimitri Arhip this time crossing the whitewash to make the score 27-10 but Davies hit the woodwork with his conversion.
Ospreys extended their lead on 41 minutes as Ben John was awarded a score from close range via the TMO, with Davies adding the extras.
And just four minutes later the Ospreys added their sixth score of the game as Dan Evans crossed, with Davies this time missing the conversion to leave the score at 39-10.
Tom James pulled a score back for Cardiff after the hour mark, with Anscombe adding a conversion for the Blues.
But the comeback was short-lived as Josh Matavesi scored the Ospreys seventh try, with Dan Biggar extending the score to 46-17.
Reynold Lee-Lo went over for another late score for Cardiff to soften the blow of their heavy defeat, with Anscombe again adding the extras off the tee.
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|Ospreys Score Card|
|Alun Wyn Jones||1||5|
|Cardiff Blues Score Card|