Melbourne, Australia - Andreas Seppi knew he couldn't relax.

Up two sets against Roger Federer, the 30-year-old Italian was eying a big upset but remained wary of the opponent on the other side of the net.

"It's never comfortable playing Roger," Seppi said in an on-court interview with a TV reporter.

He should know.

Seppi lost his first 10 matches against Federer before finally finding the all-time great's number in a monster upset on one of tennis' biggest stages.

Seppi handed the second-seeded former world No. 1 Federer his earliest exit at the Australian Open in 14 years, gutting out a four-set win in the third round on Friday that took three hours to complete and ended with one of the unheralded Italian's best shots on match point in a fourth-set tiebreak.

Following a hard serve, Seppi found himself in no man's land on Federer's return but got the ball back. It drew Federer to the net, but Seppi was able to track the next shot down in the corner, looping a forehand over Federer and down the line for a winner.

It finished off a 6-4, 7-6 (7-5), 4-6, 7-6 (7-5) win that ended Federer's run of 11 consecutive semifinal appearances at the season's first Grand Slam event.

"To beat Roger first time, especially in a Grand Slam, best-of-five, is a special moment for me," said Seppi. "Of course, at the beginning, I just went on the court to enjoy the match and to play my best tennis. I was pretty calm. I have to say, from the beginning [and] also in the important moments."

Federer hadn't lost this early at the Aussie Open since he was also ousted in the third round way back in 2001.

"[It was] just a bad day," admitted Federer. "I wish I could have played better, but clearly it was tough losing the first two. [I] had chances to get back into it. I let it slip, I mean, both times in some ways. I guess I won the wrong points out there today. I knew how important that second set tiebreak was, so clearly that hurt, losing that one. The end wasn't pretty. It wasn't easy to play with the shadow. But it was the same for both of us. [It was] just a disappointing loss."

The four-time Aussie champion -- his last win came in 2010 -- Federer aced Seppi 15 times but also committed nine double faults, including one to go down 15-30 in the 12th game of the fourth set.

The Swiss star fought back and won the game with an ace to force a tiebreak.

Federer holds a men's-record 17 Grand Slam titles, but it's the three-time ATP champion Seppi who moved on to face Aussie Nick Kyrgios.

Meanwhile, third-seeded former No. 1 Rafael Nadal got past Israeli Dudi Sela 6-1, 6-0, 7-5 and No. 6 seed Andy Murray, a three-time Aussie Open runner- up, eased to a 6-1, 6-1, 7-5 win over Portuguese Joao Sousa and will next face No. 10 Grigor Dimitrov, who battled Marcos Baghdatis for 3 hours, 27 minutes before besting the 2006 Melbourne runner-up 4-6, 6-3, 3-6, 6-3, 6-3 win.

The 14-time Grand Slam champion Nadal beat Federer in the 2009 Aussie final and is a two-time runner-up in Melbourne, including last year when he was stunned by Stan Wawrinka in the final. Nadal, of course, is the reigning French Open king.

Nadal's fourth-round opponent will be tall South African Kevin Anderson.

In other third-round action involving seeds, No. 7 former Wimbledon runner-up Tomas Berdych handled Serb and last week's Sydney champion Viktor Troicki 6-4, 6-3, 6-4 and a No. 14 Anderson dismissed No. 24 Frenchman Richard Gasquet 6-4, 7-6 (7-3), 7-6 (8-6).

Up next for Berdych will be dangerous Aussie Bernard Tomic.

Also on Day 5, the promising crowd favorite Kyrgios doused Tunisian Malek Jaziri 6-3, 7-6 (8-6), 6-1 and an all-Aussie affair saw Tomic knock out Sam Groth 6-4, 7-6 (10-8), 6-3.

The third round will resume here on Saturday, including matches for current world No. 1 Novak Djokovic, the fourth-seeded reigning Oz champion Wawrinka and fifth-seeded U.S. Open runner-up Kei Nishikori. Djokovic will take on 31st-seeded Spaniard Fernando Verdasco, while Wawrinka will encounter Finnish veteran Jarkko Nieminen and the Japanese Nishikori will be opposed by American two-time NCAA singles champion Steve Johnson.

The reigning Wimbledon champ Djokovic is a seven-time major titlist, including four Aussie crowns. He captured the title at Melbourne Park three straight years from 2011-13.

Also slated for action Saturday are eighth-seeded Canadian Milos Raonic, ninth-seeded former Roland Garros finalist David Ferrer and 19th-seeded towering American John Isner.