A powerful opening half from the hosts saw them take control and a 17-9 lead, despite a solid kicking display from Gareth Davies, with tries from Ashley Beck and a double from Natoga.
Wales’ international scrum half Rhys Webb wrapped up the bonus point quickly after the restart and Ospreys were always in control as Blues failed to fire in miserable conditions with Natoga completing his treble in the closing minutes.
Blues, now under the guidance of Dale McIntosh and Paul John, made seven changes for the fixture and recalled Alex Cuthbert and Gethin Jenkins after Welsh duty while Cory Allen returned in midfield.
But it was a difficult night for the coaching team to endure as a below par showing littered with turnovers in wet conditions saw the play-off chasing Ospreys collect maximum points and leave Blues with plenty to ponder with five league games left this season.
A wet and cold night greeted the two teams after three weeks without any league action and it was Allen who was immediately into the action with a big hit on Sam Davies to dislodge the ball in the tackle.
A big scrum from Ospreys turned over ball and a kick in behind by Jonathan Spratt forced Dan Fish to dot down for a 22 drop out. Wales half back pairing Rhys Webb and Dan Biggar then combined down the short side, but an alert tackle from Lloyd Williams averted danger.
Impressive work from Josh Navidi at the breakdown then forced an important penalty for holding on and helped Blues relieve mounting pressure from the hosts in the opening five minutes.
A stuttering lineout was not allowing Blues to find any field position and the pressure finally told on ten minutes as livewire runner Natoga and Spratt made big yards by cutting back inside before the ball was spun wide right and Beck slid over.
Blues looked to respond as Filo Paulo charged down a clearing kick from Webb and a grubber in behind from Davies was pounced upon by home full back Sam Davies before Allen could touch down. Back went play for the penalty and Davies nudged over the kick.
Ospreys went further ahead on 16 minutes when a smart kick in behind from Webb was latched onto by Natoga who smartly used his feet to hack ahead on the greasy surface and beat Fish, as he lost his footing trying to adjust, to the loose ball to score.
Blues again needed to show spirit and Gavin Evans showed great footwork and handling to explode down the middle in driving rain. But turnovers continued to hurt Blues as Ospreys repelled any danger.
Davies then slotted a long range kick, after Blues secured a scrum penalty, but it was Ospreys who were dominating possession and territory with the missed tackles mounting against Blues.
A driving lineout saw Blues make good ground down the middle and another penalty, for not releasing in the tackle, gave Davies a third successful kick of the night to cut the lead to 12-9.
The good work, though, was undone almost immediately as Blues lost the ball inside their own 22 and the hosts attacked with pace and intent. Neat handling finally saw Sam Davies flick a pass out of the tackle and Natoga crashed over.
Weather conditions continued to worsen as the half wore on with heavy rain lashing the teams, but Blues held out as they looked to regroup in the dressing room after a difficult opening half in Swansea.
Blues needed a spark at the start of the second half more turnovers at the breakdown saw momentum lost.
Ospreys continued to look menacing every time they had the ball as Justin Tipuric rattled up close before a show and go from scrum half Webb saw him look to dot down. Referee Nigel Owens went upstairs to the TMO and adjudged he had grounded the ball for the bonus point.
A long kick from Sam Davies ran horribly and pulled up short of the line, forcing Gareth Davies to hurriedly slice into touch. But Ospreys again came away with points as Biggar’s penalty put the home side 27-9 clear.
The game was beginning to get really stretched and just as Blues looked to mount a charge, with Harry Robinson and Allen looking threatening, the ball was lost as Ospreys broke with pace as they hunted more points.
Robin Copeland crashed over the line after a strong driving lineout and initial line break from Gareth Davies. But play was brought back for a knock on in the build-up as Blues had nothing to cheer.
Replacement Sam Hobbs drove up close before Paulo and Lewis Jones went close as the visitors enjoyed their best spell of the game. But it was to no avail as the visitors could find no way past a well drilled Ospreys defence.
Ospreys looked to apply the gloss in the closing minutes and a slick move down the left, with Hobbs on the floor after a heavy hit, saw Natoga complete his treble as he touched down despite a big tackle from Cuthbert.
Timeline:
10m Beck t Biggar c 7-0
14m Davies p 7-3
16m Natoga t 12-3
21m Davies p 12-6
27m Davies p 12-9
29m Natoga t 17-9
48m Webb t Biggar c 24-9
52m Biggar p 27-9
69m Natoga t Biggar c 34-9
Cardiff Blues: 15 Dan Fish, 14 Alex Cuthbert, 13 Cory Allen (Tuifua 66), 12 Gavin Evans, 11 Harry Robinson, 10 Gareth Davies (Humberstone 69), 9 Lloyd Williams (Jones 63); 1 Gethin Jenkins (Hobbs 63), 2 Rhys Williams, 3 Taufa’fo Filise (Andrews 53), 4 Chris Dicomidis (Reed 66), 5 Filo Paulo, 6 Ellis Jenkins (Cook 48), 7 Josh Navidi, 8 Robin Copeland
Replacements: 16 Kristian Dacey, 17 Sam Hobbs, 18 Scott Andrews, 19 Lou Reed, 20 Macauley Cook, 21 Lewis Jones, 22 Simon Humberstone, 23 Isaia Tuifua