But one of those defeats came in five sets in the 2009 final at Flushing Meadows, when del Potro won his only Grand Slam title and ended Federer's streak of five consecutive championships in NY. She reached her first Grand Slam semifinal since 2013.
The 19-year-old, who grew up idolising Nadal and had the Spaniard's poster pinned up on his bedroom wall was smiling from ear-to-ear as he posed for pre-match photos with his hero. Federer is, bidding for a sixth US Open and 20th major, and is playing Philipp Kohlschreiber in their round of 16 clash. Pliskova must reach the final to retain her top spot atop the WTA rankings, while on the men's side, Federer needs to win to have a shot at claiming the No 1 ranking from Nadal. Sloane Stephens, who had foot surgery in January and returned to the tour in July.
She will next face either Ukrainian fourth seed Elina Svitolina or Madison Keys of the United States.
Having been well below his best in five-set wins over Frances Tiafoe and Mikhail Youzhny in the first two rounds, Federer appeared to have shrugged off concerns over his form by easing past Feliciano Lopez.
A beaten finalist in 2016, Pliskova will next face American 20th seed CoCo Vandeweghe, who made the last eight for the first time by beating Lucie Safarova of the Czech Republic 6-4, 7-6 (7/2).
Karolina Pliskova powered her way into the U.S. Open women's quarterfinals, overwhelming American Jennifer Brady 6-1, 6-0 in just 47 minutes.
Federer, a flawless 11-0 against the German, started quietly and content to feel out his opponent but it was not long until he turned up the pressure breaking with a thundering forehand to secure the early break 4-3 and cruising to 1-0 lead.
ESPN.com noted it was the first time in Federer's career his first two matches at a Grand Slam event went to a decisive fifth set.
With the match on serve at 2-1 to the German in the second set, the razor sharp Federer tore through six successive games to take the set and 1-0 lead in the third. The top-seeded Nadal faces Alexandr Dolgopolov on Monday afternoon.
Juan Martin del Potro came back from two sets to defeat No. 6 seed Dominic Thiem.