The Blues had the elements in their favour in the first half but were unable to capitalise as the Ospreys patiently built up a head of steam.
In the second half the Ospreys got off to a flyer when prop Bethan Howell scored a try just four minutes after the restart.
With the front row of Howell, hooker Amy Lawrence and debutant Jill Richardson playing well individually and collectively, the Ospreys were able to put No8 Shona Powell-Hughes on the front foot. The Welsh representative rewarded her colleagues with a match winning try in the 59th minute.
Ospreys head coach Ben Rose was delighted with the team's success.
"The Blues started the brighter of the two teams but we gradually got on top. It was a great team performance. I thought our front row were outstanding with Jill [Richardson] doing really well in her first game for the region.
"In Kerin Lake at full back we had the best back on the field - she counter attacked really well but this was a real team effort.
"It's the first time the Ospreys have won the title and the girls fully deserve it for all the hard work they have put in. Some have forced their way into the Six Nations squad while a handful will make the Development squad. We may have just won the title but the coaching team are already looking forward to working with this group next season."
The other game between the Scarlets and Dragons was postponed.