Victoria Azarenka was left as the only top-three seed still standing in the last eight when Sharapova was scratched from the title race by Dominika Cibulkova, a day after Serena Williams had also tumbled out in the fourth round. (Agencies)
In the men's draw, the "Big Four" look poised to scrap it out for yet another grand slam crown over the next week after Nadal, Roger Federer and Andy Murray all won on Monday to join Novak Djokovic in the last eight.
Spaniard Nadal led the way with a 7-6 (7-3) 7-5 7-6 (7-3) victory over Japan's Kei Nishikori on Rod Laver Arena that was by no means as easy as the phrase "straight sets" would suggest.
The world number one had to contend with a blister on his hand, a tumble, a time violation at a crucial moment and his first losses of his serve in the tournament but most of all with some inspired shot-making from the Asian number one.
"I didn't play bad today, but I didn't play as good as I did two days ago," Nadal said, reflecting on his brilliant performance in the third round against Gael Monfils.
"But today's victory has much more value than the victory of two days ago. Because when you are playing that good, the normal thing is to win.
"When you are playing normal and the opponent is a good one, and you are able to keep winning, that has much more value."
While Nadal will meet Sharapova's boyfriend Grigor Dimitrov for a place in the semi-finals, Federer and Murray's quarter-final date ensures that at least one of the quartet of dominant men's players will go home on Wednesday.
Federer's quickfire 6-3 7-5 6-4 victory over Jo-Wilfried Tsonga was the most impressive of the day, particularly given the French 10th seed had taken him to five sets in Melbourne and beaten him at Roland Garros last year.
"I definitely felt momentum was on my side, no doubt," said the Swiss 17-times grand slam champion.
"I started the match well. Did I break first game? I think I did. I felt, alright, things are working for me tonight. Let me try to run away with it."
Murray also looked to be racing to victory against Stephane Robert, the first lucky loser to reach the fourth round in Melbourne, but blew a couple of match points in the third set and was dragged into a tiebreak, which the Frenchman won 8-6.
The Wimbledon champion took out his frustrations on his a racket, changed his shirt and then whipped through the fourth set to record a 6-1 6-2 6-7 (6) 6-2 victory.
"I dominated 95 percent of the match, and for 15 minutes didn't close the match out," said the fourth seed.
"But I still created chances, even when I wasn't playing so well at the end of that third set. So it was pretty good for the most part."
Like Murray, Sharapova missed the back end of last season because of injury and she admitted after her 3-6 6-4 6-1 defeat to Cibulkova that the tournament had probably come a little bit early for her.
"I certainly would have loved to played a little bit more before playing a grand slam, but this is the chance that I was given," said the Russian third seed, the 2008 champion here.
Victoria Azarenka was left as the only top-three seed still standing in the last eight when Sharapova was scratched from the title race by Dominika Cibulkova, a day after Serena Williams had also tumbled out in the fourth round.