The 20-time Grand Slam champion needed all his experience and determination to beat Rod Laver Arena 7-6 (16/14), 6-2, 6-2 to reach the final eight.
The 35-year-old Spanish great is in the 14th quarter-final of his 17th visit to Melbourne.
Sixth-seeded Nadal will now face third-seeded Alexander Zverev of Germany or 14th-ranked Denis Shapovalov of Canada in the quarterfinals.
“I was a little bit lucky at the end of the tiebreaker, I had my chances but then he also had a lot of chances,” Nadal said.
“Sometimes I was unlucky because the opponents were better than me.” It can be done with the best of us, https://t.co/CYsXXokXlO
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“That crazy first set was very important and so was the service break early in the second set.
“He was playing wonderful Tennis Throughout the tournament, there were wins against wonderful players, and today the first set was very difficult.
“His ball was very difficult to control, very flat, very fast and I am very happy that I escaped from it.”
Nadal is chasing the men’s record 21st Grand Slam and is reduced to the 2021 season due to a long leg injury following the Kovid-19 attack in December.
The story of the match was an extraordinary opening-set tiebreak, where Nadal had seven set points and Mannarino of France had four.
It turned out to be an epic in the boiling heat, before Nadal won 16-14 in an angry rally.
ક Don’t tell anyone… 🇪🇸 afaRafaelNadal is in his 14th #AusOpen quarterfinals! Beats World No. 5 Adrian Manner … https://t.co/4SrGCtJ9lD
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The 69th-ranked Mannarino was seen injuring his groin or abdomen in pursuit of a drop shot during a tiebreak and needed courtside treatment.
An attempt at the drain opening set was reported on Mannarino, who lost his opening service game in the second set and followed up with another in the fifth game.
With Nadal fully in command and with the task at hand, the result was inevitable.
Mannarino was also coming out of a 4 hour 38 minute fight to overtake 18th seed Aslan Karatsev in the previous round which ended early Saturday morning.
Mannarino fought the battle but Nadal managed to work towards victory to stay unbeaten after seven matches this season.