Rhys Williams's try and four penalties from the booming boot of Nicky Robinson saw the Blues edge a intense encounter in Cardiff.
A last minute penalty miss by Osprey fly half Shaun Connor gave last season's runners-up the first Welsh bragging rights of the season.
The League campaign kicked off with a spicy affair in front of a packed Arms Park crowd between two arch rivals and fittingly, the top two teams of last season.
The Blues were looking for revenge as the Ospreys pipped them to the title back in May, and Dai Young's men came flying out of the blocks.
On five minutes, the host's early pressure was rewarded through a Nicky Robinson penalty but the champions bounced back in typical fashion with a penalty of their own following a thunderous kick by Shaun Connor from just inside the Blues half.
There were feisty battles both on and off the field with the home support desperate for a winning start to the season.
One of the best match-ups was the battle between former Osprey scrum half Jason Spice, making his Blues league debut, and the man who took his place at the Liberty Stadium, Justin Marshall. Connor maintained his excellent long-range kicking with two penalties from distance to put the visitors 9-3 in the lead as the Blues were punished for offside.
But the home side gave themselves a massive boost with the first try of the match on the stroke of half-time. Powerful forward play by Tongan Maama Molitika was supported by wing Rhys Williams who touched over to bring the deficit to just one point at the interval.
Robinson and Connor kept up the enormous kicking in the second period but the Welsh stand-by player shaded the extended the Blues advantage with three huge kicks as Connor lost his nerve in the final minute.
Try: R Williams
Pens: N Robinson (4)
Pens: S Connor (5)
Blues:B Blair; R Williams, T Selley, D Hewitt, J Roberts; N Robinson, J Spice; Yapp, G Williams, G Powell, D Jones, P Tito (R Sidoli 78), M Molitika, X Rush (Capt), R Sowden-Taylor (M Lewis, 38-40)
Ospreys: L Byrne; S Terblanche, M Taylor, A Bishop, A Brew (J Vaughton 50); S Connor, J Marshall; P James, R Hibbard (B Williams 60), A Millward (C Griffiths 67), B Cockbain (capt), M Collins (M Powell 67), A Lloyd, F Tiatia, R Pugh (C Griffiths, 47-56, B Lewis 62)
Referee: T Hayes (WRU)