Germany's Mischa Zverev (Right) embraces after winning his Men's singles fourth round match against Britain's Andy Murray at the Australian Open in Melbourne, Australia on Jan 22, 2017. [Photo/IC]

He was undone by some old-school serve and volley from Zverev, who played the match of his life. Zverev will now meet 17-time major winner Federer in the quarterfinals.

In between the upsets was pretty rocky, too. Federer was down 5-1 in the first set against Kei Nishikori but found a way to fend off the 2014 US Open finalist, who was cramping and needed late treatment on his back, 6-7 (4), 6-4, 6-1, 4-6, 6-3.

It was Federer's 200th career win over a top 10 player.

He was ecstatic. "It was about staying with him. ... almost going down 6-0, I thought 'It's not going to get any worse from there,'" said Federer, on the comeback from six months on the sidelines to repair his injured left knee. "Huge win for me in my career."Murray's exit follows the second-round departure of Djokovic, beaten in the second round by No. 117-ranked wild-card entry Denis Istomin.

It's the first time since 2002 that the top two seeds in the men's draw haven't reached the Australian Open quarterfinals, and the first time at a Grand Slam since the French Open in 2004.

In their absence, US Open champion Stan Wawrinka is a growing contender after beating Andreas Seppi 7-6 (2), 7-6 (4), 7-6 (4). He'll play a quarterfinal against 2008 Australian Open finalist Jo-Wilfried Tsonga, who beat Dan Evans 6-7 (4), 6-2, 6-4, 6-4.

In the bottom half of the draw, 14-time major winner Nadal is the only remaining contender who has won a Grand Slam title.