The oft-injured Anderson, the 28th seed, took advantage of the soft underbelly of his half of the draw, one decimated by injury withdrawals and top seeds toppled early.
If someone had suggested in the beginning of the year that Roger Federer would win two Grand Slams and Rafael Nadal would take another (and possibly a second), we probably would have rolled our eyes.
'For me, it means everything to be back here in this incredible court in front of an unbelievable crowd just to be in the final and have the chance to fight for another title here is so important for me'.
After switching tactics and changing the rhythm of his serve, he went on to earn a 4-6, 6-0, 6-3, 6-2 victory over Del Potro, who had upset Dominic Thiem and Federer.
Rafael Nadal brought his "A game" on Friday at the US Open when the Spaniard, behind a bevy of bludgeoning blasts and a hyper-aggressive gameplan, ruthlessly destroyed Juan Martin del Potro.
There are two different schools of thought when it comes to Anderson: The first is that he will be overwhelmed with nerves in his first major final and freeze. That strategy could be challenging against Nadal, who is averaging just over 24 unforced errors a match in this tournament.
Following Friday's win, ESPN asked Nadal on court whether he thought a year ago - when he lost in the round of 16 in NY - that he would reach three major finals in 2017 with the chance to win two titles.
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With his path to the final eased by injuries to leading players, Anderson also became the lowest ranked grand slam finalist since Jo-Wilfried Tsonga's run to the 2008 Australian Open final when world number 38.
However, the start of the year was nearly a different tennis universe, where neither Federer nor Nadal was expected to win any more majors. He is also the first South African since Cliff Drysdale in 1965 to make this far at Flushing Meadows, and the first ex-college player since John McEnroe in 1984. Anderson is the first man from his nation to do so since Kevin Curren lost the 1984 Australian Open final to Mats Wilander.
2 - Number of unseeded winners of the U.S. Open women's title in the Open era, which began in 1968. A bazooka-serving South African, his next ace in Queens will be a tournament-leading No. 115.
Despite a 4-0 winning record over Anderson, Nadal said he will not underestimate his opponent on Sunday. "I was able to control the court a bit more, not let (Correno Busta) dictate so much", said Anderson after his semifinal win. It's great I have given myself a spot.
"I get very nervous when watching Kevin [from the stands]".