Top seed Nadal enjoyed a 7-5, 6-3, 6-3 win over Croatian veteran Ivan Ljubicic and will next face Roland Garros bogeyman Robin Soderling, the only man to have beaten the great Spaniard in Paris in 43 matches.
Fifth seed Soderling, who has reached the last two finals, losing to Roger Federer in 2009 and Nadal in 2010, beat French 18th seed Gilles Simon 6-2, 6-3, 7-6 (7/5).
Nadal, bidding for a sixth French Open title to take him level with Bjorn Borg, has looked a shadow of his usual self in Paris, shaken by the form of Djokovic, who could take his title and number one spot before the week is out.
His mood would not have been improved by knowing that the Serbian second seed was excused quarter-final duty when scheduled opponent Fabio Fognini of Italy withdrew with a torn left thigh muscle.
"There was a lot of wind today, which made it very awkward," said Nadal, before dismissing suggestions that Djokovic, who will not play until Friday, might lose the rhythm that has brought him 41 successive wins this year.
"After he doesn't lose a match all year with 40-something straight victories, you think he's out of rhythm now?" Nadal asked at his news conference.
"Today the result was very positive for me, winning in three sets without too many problems. It's fantastic to be in the quarter-finals."
Fognini, who had been due to play his first career Grand Slam quarter-final, suffered a tournament-ending injury in his marathon five-set fourth-round win over Albert Montanes on Sunday.
"It's the most difficult decision I've made. It was my first Grand Slam quarter-final and I am playing the best tennis of my career," said Fognini, the first Italian man to reach the last eight in Paris since Renzo Furlan in 1995.
Djokovic said he felt sympathy for Fognini, a player he has defeated in both of their career meetings.
"Walkover from Fognini. Bad luck for him, hope he recovers fast. Today I get to enjoy Paris in a different way," wrote the Serb on Twitter.
Soderling, who needed a fifth match point to defeat Simon for the sixth time in eight meetings, said he feels inspired every time he comes back to Paris.
"I have good memories of this tournament. I have won a lot of great matches here and I get a great feeling every time I come back," said the Swede, who famously defeated Nadal in the fourth round in 2009.
French ninth seed Gael Monfils, a 2008 semi-finalist, set-up a last-eight clash with third seed Federer after defeating Spain's David Ferrer, the seventh seed, 6-4, 2-6, 7-5, 1-6, 8-6.
Monfils had led by two sets to one when the tie was suspended on Sunday night and despite squandering three match points in the ninth and 11th games of the decider on Monday, the 24-year-old eventually held his nerve.
"I had a problem with my ankle so I was happy to come off on Sunday night," said Monfils.
"On the match points, I was a bit rushed and was vulnerable. But I told myself just to focus on the simple stuff, be aggressive and confident about the shot. This is one of the best wins of my career."
Argentina's Juan Ignacio Chela shattered Alejandro Falla's dreams of becoming the first Colombian man to reach a Grand Slam quarter-final with a 4-6, 6-2, 1-6, 7-6 (7/5), 6-2 win.
"I was sure I'd never get to this stage again because of my age," said 31-year-old Chela, who made the last eight in 2004. "Now I feel younger."
He will face either British fourth seed Andy Murray, who is carrying an ankle injury, or Serbia's 15th sees Victor Troicki for a place in the semi-finals.
Murray recovered from two sets to love down to pull level with the Serbian Davis Cup winner when darkness halted their tie. Troicki won the first two sets 6-4, 6-4 before Murray took the next two 6-3, 6-2.
The match will be played to a finish on Tuesday.
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