Sabalenka lived up to her top seeding with a 6-3 7-6 (7-3) victory in a mostly one-sided women's final to capture her fourth career major, adding a second Open trophy to her two Australian Open triumphs.
Atoning for shattering losses in this year's Melbourne Park and French Open title deciders, the Belarusian dominated the American eighth seed for much of the match, only faltering briefly late in the second set on Saturday (Sunday AEST).
"It's crazy. All the life lessons are worth it for this one," the 27-year-old said after becoming the first woman since the great Serena Williams in 2014 to go back-to-back at Flushing Meadows.
"I'm speechless right now."
Three years after taking time out from tennis following the sudden death of her father, Anisimova had been hoping to bury the demons of a 6-0 6-0 Wimbledon final defeat seven weeks ago to Iga Swiatek.
But while this crushing setback was not so humbling, the outcome was depressingly the same for the 24-year-old.
"The two finals in a row is great, but then it's super hard," Anisimova said.
"Yeah, it's been a great summer, but I think I didn't fight hard enough for my dreams today."
The much-anticipated title decider between the two biggest hitters in women's tennis failed to match the hype as Sabalenka cast aside the challenger and sentimental favourite from nearby New Jersey in one hour and 34 minutes.
Despite conjuring three break points in the opening game, Anisimova was unable to get on the board until 10 minutes into the match.
The underdog received a rousing reception from the packed crowd after finally holding serve to trail 2-1.
But Sabalenka upped the ante to reel off three straight games from 3-3 to take the first set, then storm to a 3-1 lead in the second.
Anisimova threatened a comeback after fighting back from 5-3 down to force a second-set tiebreaker.
Despite her wobbles trying to close out the championship, Sabalenka held her nerve to win an incredible 19th consecutive breaker this year to prevail on her third match point.
The champion was gracious in victory.
"I know how much it hurts," Sabalenka told Anisimova after pocketing a cheque for $US5 million.
"Reaching back-to-back finals in grand slams, you're going to win your first one. You play incredible tennis and congratulations on what you have been able to achieve after you came back."
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