A day after rain played havoc with the schedule, Sharapova's hopes of reaching a fourth successive final at Roland Garros were turned to dust in the fourth round by the dynamite forehand of Lucie Safarova, the Czech winning 7-6(3) 6-4.
An explosive quarter-final, however, awaits those lucky enough to hold Wednesday (local time) tickets for Court Philippe Chatrier after nine-time champion Nadal and world number one Djokovic set up a smoking showdown that former champion Jim Courier called "the match of the season so far."
For 10 days now, all roads at Roland Garros had been leading to this last eight collision and it became a reality as Spanish sixth seed Nadal tamed American tyro Jack Sock 6-3 6-1 5-7 6-2 shortly before Djokovic overwhelmed Richard Gasquet 6-1 6-2 6-3.
For under-the-weather Sharapova, though, Monday was a total let down.
The Russian spent the changeovers coughing and spluttering into a tissue but the second seed refused to blame health problems for her earliest Paris exit since 2010.
"I'm still a competitor no matter what. I'm going to do everything in order to go out and give it my best. I did the best I could. Today it wasn't enough, because my opponent had a different gear than I did," the 2012 and 2014 champion told reporters.
Sharapova was one of eight grand slam champions in action on day nine with Serena Williams and Roger Federer making sure they did not suffer the same fate as the Russian.
Top seed Williams relied on her famed survival instincts rather than her explosive firepower to extinguish the challenge of fellow American Sloane Stephens 1-6 7-5 6-3.
As she came back from a set down for a third match in a row, her exertions turned her hot-pink outfit into darker shade of cerise -- but that mattered little to the fashion-conscious Williams.
"I keep fighting, I never give up," a grinning Williams summed up following a performance strewn with 43 unforced errors.
Fellow 33-year-old Federer also harbours hopes of landing another title in Paris.
In the build-up to his showdown with French showman Gael Monfils, Federer tweeted a squiggly sketch of the Eiffel Tower.
While his attempt at drawing the famous Paris landmark would not look out of place in the sketch books of his five-year-old twins Charlene Riva and Myla Rose, what the Swiss produced on court was a masterpiece.
DAZZLING FEDERER
Resuming the match at one-set all, Federer dazzled Monfils with an array of spine-tingling winners for a 6-3 4-6 6-4 6-1 victory that kept him on track for a record 18th grand slam title.
"I'm pumped up to be in the quarters again. It really means a lot to me," he said.
At 33, Federer would have been relieved with such a swift conclusion to the match because, thanks to Sunday's rain-curtailed programme, he will be back on court for the third day running on Tuesday for his all-Swiss quarter-final against Stan Wawrinka.
There will be two Spaniards in the men's last eight after seventh seed David Ferrer ended U.S. Open champion Marin Cilic's run with a 6-2 6-2 6-4 romp.
His next challenge will be ending the 14-match claycourt winning streak of Andy Murray after the British third seed tamed France's Jeremy Chardy 6-4 3-6 6-3 6-2.
Wimbledon winner Petra Kvitova was barely noticed as she also slipped out, beaten 2-6 6-0 6-3 by Swiss Timea Bacsinszky.
Sharapova's exit blew open the bottom half of the women's draw, where Ana Ivanovic remains as the highest seed at seven.
While Safarova produced 19 scorching forehand winners to bamboozle Sharapova, the Russian was also left to rue double faults at key moments.
She produced a pair of misfiring serves in the first set tiebreak, another double saw her go 2-0 down in the second set and a third handed Safarova match point.
"Oh my God, I cannot say how happy I am... this is amazing," Safarova said.
