Eighth seed Anisimova won 6-7 (7-4) 7-6 (7-3), 6-3 in a match that finished just before 1am on Friday to set up a title match against top seed and defending champion Aryna Sabalenka.
"I wasn't sure I would make it past the finish line and I tried to dig deep," said Anisimova, who needed three match points to get the job done. "It was a huge fight out there today."
The US Open final comes just eight weeks after Anisimova suffered a shattering 6-0 6-0 loss to Iga Swiatek in the Wimbledon final.
The 24-year-old from Florida screamed "Let's go" and fell to her knees after winning in two hours and 56 minutes to get another shot at a maiden slam title .
Sabalenka ousted another home hope, Jessica Pegula, 4-6 6-3 6-4 in their semi as she attempts to become the first woman to claim consecutive championships at Flushing Meadows since Serena Williams got three in a row from 2012-14.
Anisimova recovered from her crushing Wimbledon final defeat to get past Swiatek in two sets in her US Open quarter-final before removing Osaka.
She became the first opponent to beat former world No.1 Osaka this late in a grand slam tournament. Before this loss, Osaka had been a combined 14-0 over her career in major quarter-finals, semi-finals and finals, with two trophies apiece from the US Open and Australian Open.
Asked what allowed her to win, Anisimova replied: "Oh, my God. I don't know. I mean, Naomi is playing amazing tennis. She's back where she belongs."
She did it by not holding anything back down the stretch, going for — and delivering — big groundstrokes that usually landed deep in the court and right where she wanted them.
Anisimova's purest-in-the-sport backhand and almost-as-good forehand helped her compile 50 winners, 18 more than Osaka.
"Sometimes, I was like, 'How are we making these shots?'" Anisimova said. "But we were."
Sabalenka's earlier win over was far closer than the straight-sets triumph she achieved over Pegula 12 months ago that gave the 27-year-old from Belarus her third grand slam title, all on hard courts.
Since then, Sabalenka was runner-up to Madison Keys at the Australian Open in January and to Coco Gauff at the French Open in June, then was eliminated in the Wimbledon semi-finals by Anisimova in July.
When this one ended on Sabalenka's third match point - after two bad errors on her initial chances - she rocked back on her heels, spread her arms and screamed.
"I had to work really hard to get this win," she said in her on-court interview after improving to 8-2 against Pegula over their careers.
"Hopefully I can go all the way again."
In the good, indoor conditions, No.4 Pegula played about as cleanly as possible in the first set and the third, making just three unforced errors in each. But in the second, that count was nine.
By the end, Sabalenka had accumulated more than twice as many winners as Pegula, 43-21.
"It means a lot," Sabalenka said of her victory.
"I will go out there on Saturday and I'll fight for every point like the last point of my life."
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