But incredibly the world number 46 pulled off a 6-4 7-6 (7/5) 4-6 7-6 (7/5) victory over the second seed, who reached at least the semi-final stage each year from 2004 to 2014.

Federer had been seeded to face either Andy Murray or Grigor Dimitrov in the quarter-finals, and both the Scot and the Bulgarian will sense the draw opening up, with possible semi-final rival Rafael Nadal also looking shaky early on in the fortnight.

Seppi captured the first set of his greatest triumph in just 35 minutes as Federer was uncharacteristically slow to find his groove.

And Seppi then seized a break early in the next, putting not only Rod Laver Arena but all of Melbourne Park on alert for a major upset.

Federer broke back but Seppi had the chance to serve for a two-set lead at 5-4 after his illustrious opponent casually disregarded a floated backhand that landed just inside the court.

A huge stroke of luck allowed Federer to break back for a second time in the set for 5-5, as a heavy net cord during a baseline battle saw the ball drop over on the Italian's side.

Just when Seppi might have been expected to wilt, instead he took the set to a tie-break with a cool drop shot.

It looked a key juncture in the contest, and Federer struck first, but he gave back the mini-break and Seppi earned set point with a cross-court forehand pass, cementing a two-set lead when the four-time champion bundled a volley wide.

Federer cut his deficit in half after an early break in the third set and solid serving thereafter proved sufficient to bite into Seppi's lead.

The fourth set was inevitably tense, Seppi going nowhere and forcing the Swiss to serve to stay in the tournament at 5-4 behind, and again at 6-5. Seppi forced deuce twice, but the world number 46 settled for a tie-break.

Again, but more so than the second set tie-break, it was hugely important and Federer again had the early mini break when Seppi netted.

A cross-court whipped forehand onto the line retrieved that advantage, and they traded mini breaks again as the tension mounted.

Very little about Federer had been convincing, but a snappy backhand was the maestro at his best and gave him two serves to level the match.

Incredibly he hooked a backhand yards wide to again give away the advantage, and two huge winners from Seppi gave him the unexpected scalp.

"I just tried to enjoying playing on centre court (Rod Laver Arena) because it's not often I get the chance," Seppi said in his post-game interview, televised by Eurosport.

"It was one of the best matches for sure otherwise I can't win against Roger.

"It's never comfortable playing against Roger, you never can feel comfortable.

"I was focusing on my service games as I was not getting many chances on his.

"The tie-break was great, especially the last point. I did not think I would get the ball. I thought it was a winner so I don't know how I hit a winner."

Seppi could potentially face home favourite Nick Kyrgios in the next round and admits he would relish the chance of facing another partisan crowd.

"It would be great, maybe on this court again, maybe again against all the people."