Federer, Nadal set up blockbuster Wimbledon semifinal
Nadal also struggled in the early going of his quarterfinal match Wednesday against American Sam Querrey before finding a higher gear to win 7-5, 6-2, 6-2.
On a hot and muggy day in London, Nishikori took advantage of some uncharacteristically erratic play by the Swiss great to break serve in the opening game of the match and go on to claim the first set.
Federer hurt his cause in that opener by committing three double faults and 12 unforced errors.
But the world No. 3 quickly put that disappointment behind him to race out to an early lead at the start of the second set, which he easily won with an impressive stat line of 100 percent first-serve points won, nine winners and one unforced error.
The Japanese world No. 7, meanwhile, went from controlling his service games in the first set to winning just five of 15 total service points in the second.
Nishikori put up a better fight over the last two sets mainly by saving numerous break points, but Federer's domination of his own service games gave him a stranglehold on the match.
With his 100th match victory at Wimbledon, the most he has recorded at any of the four Grand Slam tournaments, the 37-year-old Swiss has set up the semifinal contest against Nadal that tennis fans have been waiting for since the draw was unveiled.
Ahead of that contest, Federer told the media he expects a different match than the ones they played at Wimbledon, tennis' grass-court Grand Slam, more than a decade ago.
"(He has) improved so much over the years on this surface. He's playing also very different than he used to. Haven't played each other in a long, long time on this surface. He's serving way different. I remember back in the day how he used to serve, and now how much bigger he's serving, how much faster he finishes points," the Swiss said.
Like Federer, the Spaniard also got better as his quarterfinal match went on.
After struggling repeatedly to hold serve in the first set, including squandering a chance to serve for the first set at 5-4, Nadal found another level that Querrey could not match.
The 33-year-old world No. 2 particularly improved on his second-serve points as the match wore on, winning just 38 percent of those points in the first set but then 60 percent in set two and a whopping 73 percent in the third set.
Querrey, for his part, threw down 22 aces (14 of them in the first set) but won only 28 percent of his second-serve points for the match, as Nadal's edge in the athleticism and mobility departments proved decisive.
When Federer and Nadal meet in Friday's semifinals, it will be their first match at Wimbledon since the 2008 final, when Nadal held off a thrilling comeback by the Swiss to win 6-4, 6-4, 6-7 (5-7), 6-7 (8-10), 9-7.
That contest was the longest final ever at Wimbledon and - considering the occasion and the pedigree of the two competitors - is widely considered the greatest match in tennis history.
Prior to that match-up, Federer - winner of a record eight Wimbledon men's singles titles - had defeated Nadal in the 2006 and 2007 finals at the All England Club.
The legendary status of Federer and Nadal has only increased since 2008, with the Swiss now holding the record for most Grand Slam men's singles titles with 20 and the Spaniard currently in second place all time with 18.
The winner of the Federer-Nadal blockbuster, however, may not even be the favorite in Sunday's final.
Serbian world No. 1 Novak Djokovic was in sublime form in brushing aside Belgium's David Goffin on Wednesday and will be the heavy favorite when he takes on Spain's Roberto Bautista-Agut in Friday's other men's singles semifinal.
Djokovic routed Goffin 6-4, 6-0, 6-2 and Bautista-Agut topped Argentine Guido Pella 7-5, 6-4, 3-6, 6-3 in Wednesday's two other men's quarterfinal matches.
In mixed doubles, the star pairing of British former men's singles world No. 1 Andy Murray, who is making his way back from a serious hip injury, and American women's singles great Serena Williams came up short on Wednesday.
Murray and Williams lost to the top-seeded team of Brazil's Bruno Soares and the United States' Nicole Melichar 6-3, 4-6, 6-2 in the third round.