Kerber won a grueling first set, then eased to victory Tuesday against Vinci in New York, 7-5 6-0, to advance to the semifinals, where she will be joined by an ultra-sharp Gael Monfils. Monfils progressed in the men's draw by downing an understandably fatigued countryman, Lucas Pouille, 6-4 6-3 6-3, to keep alive France's chances of producing a first men's grand slam winner since 1983.
Twelve months ago, Vinci engineered one of the biggest surprises in tennis history by defeating Williams in the semifinals to end the American's bid to become the first player since Steffi Graf in 1988 to achieve a calendar-year grand slam.
Topping the second-ranked Kerber wouldn't have been as much of a shock -- but still would have been plenty unexpected given the German won her first major this year after overcoming Williams in the Australian Open final
in January and tested her in July's Wimbledon final
. Kerber, too, won silver in singles at the Olympics in Rio.
Kerber eventually figured out how to cope with Vinci's unorthodox game that includes a wicked backhand slice -- the eighth-ranked Italian will rue not serving out the first set at 5-4 -- and will be assured top position in the rankings on Monday if Williams does not reach the final.
Williams, who on Monday became the all-time leader in grand slam wins, plays Simona Halep in their quarterfinal Wednesday.
If, as anticipated, Kerber and Williams face off in Saturday's final, the winner is No. 1 on Monday. As it stands, Williams sits atop the rankings for a 186th consecutive week this week to tie Graf, Kerber's idol, for the all-time women's lead.
Kerber, who missed out on the top ranking when she lost in the final in Cincinnati last month, was trying not to think too much about potentially becoming No. 1.
"This would mean a lot to me," Kerber told reporters. "When I was a kid I was always dreaming to being the No. 1. Let's see. There are still matches to go.
"I'm looking forward to play, first of all, my next match. If the day will come, it will be amazing."
She will face former No. 1 Caroline Wozniacki -- Williams' close friend -- in the last four. The Dane beat unseeded Latvian Anastasija Sevastova 6-0 6-2 to reach the semis at a grand slam for the first time since losing the 2014 US Open final against Williams.
Pouille had won three straight fifth sets at the US Open -- no man in the Open Era has won four in a row at any major -- including a fifth-set tiebreak over Rafael Nadal on Sunday. He can strike winners virtually anywhere on the court.
But all the long matches took their toll. Monfils didn't try to overplay and served well, not conceding a break point. Not even a brief stoppage to put the roof on Arthur Ashe affected the newly turned 30-year-old. Monfils, yet to drop a set, got to his second grand slam semifinal after the 2008 French Open.
Monfils is seeking to become France's first men's finalist at the US Open since 1993. However, his next opponent is world No. 1 and defending champion Novak Djokovic, who progressed when French ninth seed Jo-Wilfried Tsonga retired after losing the opening two sets in Tuesday's night session.