Djokovic had to battle through a 4-hour, 9-minute match against ninth-seeded Stanislas Wawrinka before finally prevailing 2-6, 7-6 (7-4), 3-6, 6-3, 6-4 in the day's first semifinal at Ashe Stadium, gaining the New York title match for the fourth straight year.
The Serbian star turned the tide during an epic third game in the fifth set, surviving 12 deuces and pulling off five break-point saves en route to a 2-1 lead.
Djokovic, who retained his No. 1 ranking with Saturday's triumph, will be seeking a second U.S. Open title to add to his 2011 victory in Monday's final, where he'll meet Nadal in the championship tilt for the third time in four years.
The Spaniard -- also seeking his second U.S. Open title -- moved on with a 6-4, 7-6 (7-1), 6-2 defeat of eight-seeded Frenchman Richard Gasquet in the late semifinal.
With the win, Nadal improved to a career-best 21-0 on hard courts this season and has reached the final for the 12th time in his last 13 tournaments and is looking for his 10th title of the year.
Djokovic defeated Nadal earlier this year but trails him 21-15 in all-time meetings.
"Well, it's always the biggest challenge that you can have in our sport now," Djokovic said of playing Nadal. "I mean, he's the ultimate competitor out there. He's fighting for every ball and he's playing probably the best tennis that he ever played on hard courts."