The Australian, given a wild card for this event at Carlsbad, beat the top seed 6-2 6-3 to land her first title since she was victorious at Flushing Meadows in 2011.
It was also the 29-year-old's first success over Azarenka after defeats in all eight of their previous contests.
Stosur's ability to stave off the threat of being broken proved decisive - she saved 11 of 12 break points faced on her way to wrapping up victory in an hour and 23 minutes.
Azarenka was certainly not at her best at Omni La Costa resort and the game was summed up when, facing the first of two match points, the Belarusian hit a backhand wide - her 32nd unforced error.
This year's US Open starts on August 26.