The native of Minsk, Belarus, took full advantage of the gimpy two-time champion by winning 10 of the match's final 11 games.
Williams, the top-ranked player in women's tennis, clearly was hampered by a left leg injury that limited her power and mobility.
The 19-year-old Azarenka captured her third tournament this season after winning the Brisbane (Australia) International in January and the Regions Morgan Keegan Championships at Memphis in February.
"For me it was such an honor to play (Serena)," Azarenka said after the 72-minute victory. "I am so happy to play against her and to beat her (and) I'm believing in myself more."
Azarenka pocketed $700,000 and rose to 23-2 this season.
"I'm not one to make excuses," Williams said. "I give Victoria all the credit today."
Copyright 2009 by United Press International.