Azarenka, who reached the final here last year, defeated Tereza Martincova in the first round, winning the final eight of games of the match and Jasmine Paolini in the second round.
This is the fifth time Azarenka and Muguruza will play with the head-to-head at two wins apiece. They were scheduled to meet in the Doha semifinals, but Azarenka gave the Spaniard a walkover.
Their last match on hard courts was the 2019 Monterrey final in which Muguruza won 6-1, 3-1 before a mid-match retirement by the Belarusian. Their last completed hard court match went the way of Azarenka in Miami in 2016.
Both players are very aggressive off of the ground and will want to dictate and look to attack each other's forehand. Their backhand is clearly their strength and they will try to use it to get on top in the rallies.
Muguruza possesses the better serve as she is more consistent with it and now applying topspin and slice, has cut down on her double faults. Azarenka will need to protect her own serve well, especially the second, which is not very good.
Control of the baseline will be key as Azarenka will look to move Muguruza around the court due to her excellent mobility and she will want to go down the line, an area the Spaniard is not usually hitting to.
As the Belarusian likes to take the ball early when in rallies, Muguruza will want to take time away from Azarenka. Neither player is adept at net, but the Spaniard probably gets a slight edge in that department.
This is a very even match with two players who play very similar styles. Muguruza is probably a very slight favorite despite never playing all that well at Flushing Meadows, the only major where she has never reached the final.
However, Azarenka is mentally very strong and has a track record here superior to her opponent, reaching three finals and while it would be no surprise to see Muguruza win this, back the player who has performed better in these conditions in a very, very close one.
Prediction: Victoria Azarenka in three extremely close sets