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For 23-year-old Sinner, it was a 55th match win of the season and sixth title.
Sabalenka won her first title at Flushing Meadows a year after coming up short in the final.
It's the first time in 15 years that an American man has reached a major final and both Fritz and Tiafoe wanted to be the one to break the barren streak.
Playing in her first major semifinal, Pegula was made to look like a novice by Muchova in a disastrous opening set, but somehow turned the tables on the unseeded Czech.
Pegula looked in cruise control in the second set as she broke Swiatek again in the third game.
The 44-year-old Bopanna had also lost in the men's doubles.
Fritz seized back momentum in the third set and closed out the match in a fourth-set tiebreak.
Swiatek showcased her all-court game in a straightforward 6-4 6-1 win over Russian Liudmila Samsonova to open the evening session.
The second-seeded Bopanna-Ebden pair lost to the 16th seed Argentine combo of Maximo Gonzalez and Andres Molteni in 66 minutes.
The sixth-seeded American Pegula, who struggled with injuries earlier in the year, produced her best form of the tournament so far.
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