The Liberty Stadium outfit are now unbeaten in five games against their Cardiff counterparts who last emerged victorious in this fixture almost seven years ago.
Both sides were without key Welsh internationals as Warren Gatland's side prepare for their final autumn international against Australia this weekend, but it didn't seem to affect the hosts.
They were quick out of the blocks and a charge down from George Stowers allowed Kahn Fotuali'i to break down the left, but he was dragged into touch.
Ospreys' pressure, though, resulted in a ninth-minute penalty easily dispatched by Matthew Morgan.
Moments later they increased their lead through King, the second row receiving the ball after good work from Joe Bearman and Fotuali'I to go over in the corner.
Morgan added the conversion but missed a drop goal on 15 minutes as Tandy's men looked to make the most of their enterprising start.
Morgan's boot was again wayward as the Wales U20 fly-half missed a penalty from the same distance as his first - but he made no mistake with his third, extending Ospreys' lead to 13-0.
Up until this point the Blues had barely been in their opponents' half, but a half-break by Andries Pretorius, on as a fifth-minute replacement for Robin Copeland, gave Ceri Sweeney the chance to add three points of his own.
Morgan and Sweeney exchanged a penalty each before half-time which gave the hosts a 13-6 lead at the break.
Within a minute of the restart Ospreys extended their lead through Fussell's try.
The full-back latched on to a beautifully weighted kick from wing Ross Jones and crossed in the corner to all but seal the game.
Rhys Patchell reduced Cardiff's arrears with a neatly taken penalty and Sam Lewis' yellow card for offside offered them a potential route back into the game.
Patchell notched the long-range penalty which took the Blues within 11 points but Morgan again followed suit on the hour mark to keep them at arm's length.
But it was the Ospreys who looked the more likely to add to the scoreline - Eli Walker made a brilliant break and was only halted by Josh Navidi who received a yellow card for deliberately slowing the play down.
Walker almost made his way into the corner as the game entered its closing stages, but a superb covering tackle from Lloyd Williams could only delay the inevitable as Allen went over in the final minute, but it wasn't enough for the bonus point.
|Ospreys Score Card|
|Cardiff Blues Score Card|