Zverev will face either No.8 seed Ben Shelton or the 11th-ranked Frances Tiafoe, who play later on Friday (Saturday AEST) for the right to give the US a man in the decider. Both have been semi-finalists in Flushing Meadows but neither have reached a major final.
The US is still seeking its first men's grand slam champion since Andy Roddick won in New York in 2003.
"Hopefully I can not make the American dream come true on Sunday," Zverev said in his post-match on-court interview.
Zverev finally broke through at the French Open this year and followed by reaching the Wimbledon final, where he lost to Jannik Sinner. The German is 24-2 in grand slam matches this season.
"Sometimes just things go your way and I feel like I've had a lot of struggles at the major level," Zverev added.
"I was so close so many times, and maybe this year God has said that this is going to be your year and just enjoy the time on the court."
Now he will try to win the title that he still can't believe he let get away in 2020. Zverev won the first two sets against Dominic Thiem but then lost in a fifth-set tiebreaker, as Thiem became the first man to win the US Open title after dropping the first two sets of the decider since 1949.
Zverev was solid after going up two sets this time, and has won 13 consecutive sets after becoming the first No.1-seeded man to play five-setters in each of the first two rounds of a major.
Khachanov was trying to reach his first major final after a surprising run in New York. He arrived with a losing record for the season but went on to reach his third grand slam semi, including second at the US Open.
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