World number two and top seed Federer defeated Germany's Florian Mayer 6-0, 7-6 (7/1) as he continues his build-up to an assault on an eighth Wimbledon title.
Federer required just 19 minutes to take the first set against Mayer before going on to conclude the tie in a little over an hour. Karlovic battered his way into the semi-finals by smashing 45 aces past a bewildered Tomas Berdych en route to a 7-5, 6-7 (8/10), 6-3 victory.
"I'm extremely happy about the record," Karlovic said of his battery of aces, a new record in a best-of-three set match.
"Hitting aces helps a lot, you can avoid the volleys. I was surprised when I was told on court after the match how many aces I hit. I didn't know it was that many. Hopefully I can continue like that in the semi-final."
His record came just two days after Germany's Sabine Lisicki blasted 27 aces in a match in Birmingham -- a new record for the women's tour.
Second seed Nishikori will take on the winner of the match between Frenchman Gael Monfils and Italy's Andreas Seppi. Nishikori, 25, took two and a half hours to make the final four for the second year running.
Last year, after beating Monfils in the quarters, Nishikori was defeated by Federer, who went on to win the tournament for a seventh time.
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