The Belarusian served for the title against Williams 12 months ago, but the American fought back to win 6-2 2-6 7-5.
Williams has since replaced Azarenka as world number one, thanks to a dominant year, which has seen her claim titles in Rome, Toronto, Bastad, Madrid, Charleston, Miami and Brisbane, as well as winning her 16th Grand Slam in Paris.
Azarenka has won just three of her 15 all-time matches against Williams, with every one of those victories coming in finals.
The 24-year-old, who has a 50% record in finals against Williams, tends to raise her game on the big stage.
She will certainly have to do that on Sunday because Williams will be a comfortable winner if the match follows recent form.
Azarenka's serve has been broken 19 times in this year's tournament, while Williams has only lost 16 games, winning all six of her singles matches in straight sets.
High street bookmakers Ladbrokes, Coral and William Hill have all made Williams a heavy 1-4 favourite, while Azarenka is widely available at 3-1.
Sports Mole prediction:
Serena will become the ninth woman in the Open era - after Margaret Court, Billie Jean King, Chris Evert, Martina Navratilova, Steffi Graf, Monica Seles, Venus Williams and Kim Clijsters - to successfully defend her singles title in New York.
She might drop a set, but ultimately her superior strength, both mental and physical, will see her prevail and win her 17th Grand Slam as an individual.