Del Potro, seeded sixth, topped the world No. 1-ranked Nadal 6-2, 6-4. It was the first time since 2009 -- when del Potro stopped Nadal 6-2, 6-2, 6-2 in the semifinals of the U.S. Open -- that del Potro beat Nadal.
He'd lost their last four meetings, including a three-set defeat in the final at Indian Wells, Calif., this year.
Del Potro raced out to a 4-0 lead over Nadal Saturday and finished with three breaks while saving all six of the break chances Nadal had. Del Potro fired off five aces and was good on 83 percent of his first serves.
The win assured del Potro of an invitation to the ATP World Tour Finals.
It was only the fifth loss this year for Nadal and just the second time in 15 tournaments that he didn't reach the finals. He was beaten by Djokovic in the championship match last week at Beijing but still overtook Djokovic for the No. 1 spot in the rankings.
Djokovic, seeking to defend his Shanghai Masters title, was a 6-2, 7-5 winner over seventh-seeded Jo-Wilfried Tsonga Saturday. He finished with five breaks and won more than half (37-of-52) of the points off Tsonga's serve.
Djokovic is 9-3 all-time versus del Potro and has won two of their three meetings in 2013. Their most recent match was a stunning five-set performance in the Wimbledon semifinals, which Djokovic won.
Djokovic will be going for his fifth title of the year. He has two second-place finishes (Wimbledon and the U.S. Open). Del Potro is 3-1 in finals in 2013.
The Shanghai Masters champion will take home $729,725 and the runner-up will earn $357,800. Nadal and Tsonga each picked up $180,075 as semifinalists.
Notable deaths of 2014 [PHOTOS]