Andrey Rublev beat no. 9 seed David Goffin 7-5, 7-6 (5), 6-3 to become, at 19, the youngest male U.S. Open quarterfinalist since Andy Roddick reached the round in 2001.
Keys, who rallied from a 4-2 deficit in the third set, is in the quarterfinals of the U.S. Open for the first time, while Svitolina's chance of obtaining the No. 1 world ranking following this tournament disappeared.
This was the second time this year that Vandeweghe has beaten a reigning world No 1 following her victory over Angelique Kerber in Melbourne.
Vandeweghe broke Pliskova's serve to take a 3-1 lead in the second set, but Pliskova broke back to make it 3-2.
Though Dolgopolov is unseeded, he had won two of the last three meetings with Nadal.
Former champion Juan Martin del Potro, the No 24 seed, faced sixth-seeded Dominic Thiem, with the victor getting Federer if the five-time champion can improve his 31-1 record in night matches at Arthur Ashe Stadium.
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Nadal is trying for his first U.S. Open quarterfinal appearance since winning the Grand Slam tournament in 2013.
1 Karolina Pliskova of the Czech Republic on Wednesday to advance to her first career U.S. Open semifinal. Vandeweghe was on top from the start of the tie-break and won it 7-4 as Pliskova lost the last two points with unforced errors. "But I just felt much better". "If I'm hitting my shots, I'm definitely doing a lot better job in the scoreline than she is and vice versa". However, Vandeweghe holds a 2-1 edge in head-to-head matches with Pliskova.
Pliskova, who had to save a match point to beat China's Zhang Shuai in the second round, needed to fight back from breaks down in both sets to keep her challenge alive.
Federer brings an 11-0 record against No. 33 seed Philipp Kohlschreiber into their night matchup. Vandeweghe, a NY native who moved to California with her mother as a child, is the third American woman to earn a semifinal berth here.
Karolina Pliskova is coming off a straight sets win over Jennifer Brady that took 13 games to decide.
In the next round, Kanepi will play against the Ukrainian Elina Svitolina, the American Madison Keys.