The 28-year-old left-hander, who won the Australian Open in January and was Wimbledon runner-up in July, is the first German woman to reach the final in New York since Steffi Graf in 1996.
She will emulate Graf as US Open champion if she gets the better of Karolina Pliskova, who stunned Serena Williams 6-2 7-6 (7/5) in her semi-final, in Saturday's championship match.
Graf is also the only other German woman to achieve the top ranking.
The German leads Pliskova 4-3 in their head to heads, but the Czech won their most recent meeting in the Cincinnati final last month.
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Just moments after becoming the oldest first-time world number one, Kerber raced out of the blocks against the Dane, a two-time runner-up at the tournament.
Two breaks of serve gave her a 4-0 lead after just 15 minutes, conceding only five points in the process and she had two more break points in the fifth which a desperately scrambling Wozniacki saved to finally get on the board.
Wozniacki saved two set points in the ninth game but the German left-hander secured the opener on serve at the next time of asking.
Wozniacki, down at 74 in the world after missing almost three months of the season with an ankle injury, had refused on the eve of her fifth semi-final in New York to dampen speculation that she was on the brink of announcing her retirement.
She certainly appeared to have her mind elsewhere as she slipped 2-0 down in the second set before a 27-shot rally in the third game helped her open her account.
It was a brief respite as she then broke for the fifth time in the match to march into a third Grand Slam final of the year.
Wozniacki at least has the consolation of knowing her surprise run to a fifth semi-final in the city where she keeps a second home will translate to a place back in the world top 30.