That honour falls to unheralded Albert Ramos-Vinolas who reached his first Grand Slam last-eight with a 6-2, 6-4, 6-4 defeat of Canadian eighth seed Milos Raonic.
Third seed Wawrinka, for his part, saw off Serbia's Viktor Troicki 7-6 (7/5), 6-7 (7/9), 6-3, 6-2 for his 11th straight win in the year's second Grand Slam.
"It was far from easy with tough conditions -- heavy and cold, but I am happy to have come through it," 31-year-old Wawrinka said.
"It was a big battle, but I was able to stay calm and win this match."
It was Wawrinka's fifth win in five meetings with Troicki whose challenge fizzled out after he required treatment for a right thigh injury at 4-1 down in the third set.
Ramos-Vinolas, 28, had never got beyond the second round of any major before this Roland Garros and had failed to win a match at the tournament since 2011.
But the world number 55, who is only his country's ninth best player, ensured a left-hander from Spain would be in the last-eight after the injury-enforced withdrawal of nine-time champion Nadal.
"I had lost four times in a row here so I am very happy," said the shock winner who had also won just four matches in his entire career at the majors before coming to Paris.
"I played a great match. I think the cloudy conditions helped me as they made the court slower."
He trails Wawrinka 6-0 in career meetings including last week in Geneva where he won just two games.
"Wawrinka is the titleholder. He's hugely powerful. Last week I played him, and he won very easily," said Ramos-Vinolas.
"He didn't leave any opportunity for me to play my tennis. But this is another tournament."
Raonic had been bothered by a left hip injury in the last round and the 25-year-old was obviously under-powered on Court Suzanne Lenglen.
With John McEnroe, who has agreed to work with him on his Wimbledon campaign, watching from the stands, Raonic was broken twice in the first set.
He was a break to the good at 2-0 in the second but Ramos-Vinolas roared back to claim a two-sets lead.
The Spaniard had only ever defeated one other top 10 player before Sunday and that was the impressive scalp of Roger Federer in Shanghai in 2015.
He was soon to make it two when he broke Raonic for a 5-4 lead in the third set and claimed the tie on a third match point in a seven-minute 10th game.
The Spaniard finished with just 13 unforced errors compared to 38 for the big Canadian.