Williams is looking to win a fourth singles title in the Big Apple, while Azarenka is hoping to get her hands on a first trophy in New York following her maiden Grand Slam triumph in Australia at the start of the year.
Sports Mole takes a look at the two players as they battle it out for the final Grand Slam of the season.
Previous best at US Open:
Azarenka: F 2012
Williams: Winner 1999, 2002, 2008
Record in 2012:
Azarenka: W48, L7
Williams: W46, L4
Head to head: Azarenka 1-9 Williams
Where will the match be won and lost?
Azarenka will have to play arguably the match of her year when she takes on Williams inside the famous Arthur Ashe Stadium. Despite the Belarusian being top of the world rankings, there is no doubt in anybody's mind that the American is the best women's player on the planet right now.
However, Azarenka is known to produce some of her best tennis when her back is against the wall and that is almost certain to be the situation on Saturday.
That said, if Williams plays anything like she did in her 6-1 6-2 hammering of Azarenka in their recent Olympics semi-final then it will be Grand Slam number 15 for the 30-year-old.
Sports Mole says: Serena to muscle her way through in three.