On the women's side, defending champion Kim Clijsters also advanced to the fourth round.
Neither the four-time Australian champion Federer nor 2009 titleholder Nadal have dropped a set, although Federer's path has been made easier by a walkover win in the second round.
The longtime rivals played back-to-back matches at Rod Laver Arena on Friday. Nadal, his right knee still taped from a recent injury, showed no problems while moving briskly around the court in a 6-2, 6-4, 6-2 win over qualifier Lukas Lacko.
Federer followed in the marquee matinee program by beating Ivo Karlovic 7-6 (6), 7-5, 6-3, saving a set point in the tiebreaker with a scrambling lob over the 6-foot-10 Croatian.
"He gave me a second serve and gave me a slight chance," Federer said. "Might have had a little bit of a lucky volley. ..."
"It was unlucky ... one in a 100 that I'm going to lose that point," Karlovic said. "I didn't really expect him to do that. I was there, I just miscalculated how much I was jumping. If I would have won that, everything would be different, but that's life."
Nadal had few dramas in his match against Lacko, which is just the way he wanted it. He felt a sharp pain in his knee while sitting in his chair in his hotel on the weekend, an innocent enough movement he initially feared would cause him to withdraw from the tournament.
Three matches later, Nadal says "the knee is fine ... being in the fourth round without losing a set, it's fantastic news."
Nadal will next meet fellow Spaniard Feliciano Lopez, who beat No. 16 John Isner 6-3, 6-7 (3), 6-4, 6-7 (0), 6-1 to put the last U.S. man out of the draw.
It is the first time since the start of the Open Era in 1968 that no American men have reached the fourth round at the Australian Open, although no Americans entered the tournament in 1972 and 1973. The last American to win the Australian Open was Andre Agassi in 2003, his third win in four years at Melbourne Park.
"It's very ugly, to be honest, to have no one in the round of 16 ... very disappointing, not a good effort from the Americans," Isner said. "We've got to try to rectify that next time the big tournaments roll around."
No. 7 Tomas Berdych beat No. 30 Kevin Anderson of South Africa 7-6 (5), 7-6 (1), 6-1 and will next play No. 10 Nicolas Almagro of Spain, who beat 21st-seeded Stanislas Wawrinka of Switzerland 7-6 (2), 6-2, 6-4.
Germany's Philipp Kohlschreiber defeated Alejandro Falla of Colombia 6-3, 6-2, 7-6 (3) in the other early third-round match, with two more matches scheduled for Friday night.
Defending champion and top-seeded Novak Djokovic and fourth-seeded Andy Murray, who has lost in the final at Melbourne Park the last two years, play their third-round matches Saturday, with a Djokovic-Murray replay only possible in the semis.
On the women's side, top-seeded Caroline Wozniacki also has not dropped a set in advancing to the fourth round as she continues her quest for a first Grand Slam title. She beat Monica Niculescu of Romania 6-2, 6-2 Friday, and third-seeded Victoria Azarenka defeated Mona Barthel 6-2, 6-4.
It's the toughest half of the women's draw. Wozniacki could face Clijsters in the quarterfinals, but before Clijsters gets that far, she might have to beat French Open titlist Li Na of China.
With Li still to play Friday against Anabel Medina Garrigues of Spain, Clijsters did her part by advancing to the fourth round with a 6-3, 6-2 win over Daniela Hantuchova.
"I won, so that's the most important thing," Clijsters said. "I definitely wasn't playing my best tennis."
Clijsters' only loss to Hantuchova in 11 matches was at Brisbane two weeks ago when she withdrew with a hip injury in the second set of their semifinal.
On Saturday, the two biggest threats in the other half of the women's draw, five-time champion Serena Williams and 2011 Wimbledon winner Petra Kvitova, play for a spot in the last 16.
Wozniacki, who needs to reach the quarterfinals to have any chance of retaining the No. 1 ranking, wasted one match point and was broken when she was serving for the match. But she broke back immediately to ensure she moved into a final 16 encounter against former No. 1-ranked Jelena Jankovic, who beat American Christina McHale 6-2, 6-0.
Azarenka, who beat Li to win the Sydney International last week, has only lost eight games at Melbourne Park and remains one of three women who can overhaul Wozniacki for the top ranking at the Australian Open.
The 22-year-old from Belarus will next meet Czech player Iveta Benesova, who beat Russian qualifier Nina Bratchikova 6-1, 6-3.
Azarenka was annoyed with herself for needing five match points to finish off Barthel, who was on a 10-match winning run in Australia after capturing her first title at the Hobart International last week as a qualifier.
"I've been playing in the end not brave enough to finish the match. ... I had to get a little," angry, Azarenka said.