While fans flocking to Flushing Meadows have been yearning for a final clash between Alcaraz and Jannik Sinner, the duo have to clear one more hurdle before realising that dream, with the Italian facing Felix Auger-Aliassime in the other last-four showdown.
While Alcaraz has beaten Djokovic in two Wimbledon finals, the Serb has repeatedly claimed bragging rights on hard courts.
Djokovic will do everything in his power to extend that record to 4-0 on Friday in a battle that again pits the old guard against one of the standard-bearers of a new generation.
Chasing a second crown in New York, world number two Alcaraz will have revenge on his mind after falling to the Serb in last year's Paris Olympics final and also in the Australian Open quarter-finals in January.
"We all know Novak's game," Alcaraz said. "I know he's hungry. I know his ambition for more, so let's see.
"I know I played a lot of times against him. I really want revenge. That's obvious."
Djokovic is chasing an unprecedented 25th Grand Slam crown and while the four-time US Open champion has reached the semi-finals at every major this season, he has failed to cross that hurdle each time.
The 38-year-old has admitted his body is feeling the physical toll of playing best of five-set matches. He has not won a major since 2023 in New York, with a modest ATP 250 title in Geneva standing as his lone trophy this season.
"Would love to be fit enough to play and to play potentially five sets with Carlos," Djokovic said after his quarter-final win over Taylor Fritz. "I know that my best tennis is going to be required.
"I like to play the big matches on a big stage. It's just that I'm not really sure how the body is going to feel in the next few days."
Djokovic holds a 5–3 lead in their head-to-head, yet the 22-year-old Alcaraz arrives in form with a tour-leading 59 wins and six titles this season.
World number one Sinner will enter his contest with Canada's Auger-Aliassime as the clear favourite as he looks to extend his unbeaten streak at the hard-court majors to 27 matches.
A resurgent Auger-Aliassime is enjoying his best Grand Slam run in four years and will be determined to prove that his revival is no temporary spark.
Sinner has been almost untouchable in New York, with only Denis Shapovalov taking a set off him in the third round.
The top seed is bidding to reach a fifth successive slam final, having won in Melbourne and Wimbledon this season. He was also one point away from claiming a third, having squandered three match points in the Roland Garros final against Alcaraz.
"These are very special occasions. Finding myself again in the semis of a Grand Slam, it's a great, great achievement," Sinner told reporters.
"I feel like that since two years now and in Grand Slams, I really like playing best-of-five. I know my body a little bit better, so I'm very happy and pleased to be again in the semis."
Auger-Aliassime rediscovered the fearless brand of tennis that first took him to the US Open semi-finals in 2021, securing wins over Top 10 opponents Alexander Zverev and Alex de Minaur.
Auger-Aliassime leads their head-to-head 2–1, but the Canadian was dismissed in their most recent meeting in Cincinnati last month, winning just two games.
"What to say about Jannik's game? He's been obviously untouchable at times... I need to play good tennis," the 25-year-old said. "I need to play at a high level in two days and then next round as well. There is no other way."