Federer eased into his 12th Wimbledon quarterfinal with a 6-1, 6-4, 6-4 win over Tommy Robredo, a victory headlined by a perfect second set.
Australian Open champion Wawrinka, the fifth seed, made his first last-eight date at the All England Club at the tenth attempt by seeing off Spain's Feliciano Lopez 7-6 (7/5), 7-6 (9/7), 6-3.
Federer will start as overwhelming favourite having a 13-2 record over his 2008 Olympic Games gold medal partner.
But Wawrinka won their last encounter on clay at the Monte Carlo Masters final in April and the two have never met on grass.
Federer allowed fellow 32-year-old Robredo just three points off his serve in the first set and then none at all in the second with the 17-time Grand Slam title winner claiming 20 out of 20 points on service.
In all, Robredo won just 14 points on the Federer serve as the Swiss star went level with Boris Becker in joint second place for most match wins at the tournament on 71.
It was Federer's 11th win in 12 meetings with 23rd seed Robredo and avenged his loss to the Spaniard in the fourth round of the US Open last year.
Federer finished with 11 aces and 41 winners and has still to drop a set in the tournament in marked contrast to 12 months ago when he was knocked out in the second round.
"I am very happy with the way I played today," said Federer.
"Tommy got better as the match went on," the Basel native said.
"I had a great first week and now I have started the second week well," he said.
Federer said he felt he was serving, returning an moving well.
"I feel OK on court," he said.
"I don't worry about what the press or the experts might say.
"My game is right there as long as I don't have any hiccups or letdowns."
The first set of the Wawrinka/Lopez clash saw the 100th tiebreak of the men's tournament at this year's Wimbledon — the first time in history that the number of tiebreaks at a Grand Slam has reached triple figures in either the men's or the women's event.
The two men were then locked in a heated discussion at the net at the end of the tie, although Wawrinka attempted to play down any bad feeling.
"It was nothing big," Wawrinka said.
"It was just a few things about the match, he said it wasn't anything against me."
Later in the day, world number one Nadal was sent crashing out of Wimbledon by Australian 19-year-old Nick Kyrgios in a upset match decided in four sets (7-6 (7/5), 5-7, 7-6 (7/5), 6-3).
Kyrgios, ranked just 144th, became the first wild car entry to make the quarterfinals at Wimbledon in ten years.
He faces Canada's Milos Raonic for a place in the semifinals against the winner of the Swiss showdown.
His victory has boosted Federer's hopes of an eighth title, as the Swiss was seeded to meet Nadal in the semifinals.