The Spaniard took command from the outset to win the quarterfinals against Wawrinka 6-2, 6-3, 6-1.
Nadal, who celebrated his 27th birthday on Monday earlier beat the Swiss in the final of the Madrid Masters last month.
Wawrinka’s loss comes a day after fellow Swiss Roger Federer was knocked out of Roland Garros by Frenchman Jo-Wilfried Tsonga.
"I think today I played my best match of this year at the tournament," said Nadal who now boasts a 10-0 record against Wawrinka.
In the other quarter-final match on Wednesday, world number one Novak Djokovic beat German Tommy Haas in three sets, 6-3, 7-6 (7-5), 7-5.
The results set up a blockbuster semi-final between the Serbian and Nadal, who is seeking to win his eighth French Open title.
Friday's clash will be the 35th meeting between the two with Nadal holding a 12-3 lead on clay.
But Djokovic beat the Spaniard in the Monte Carlo Masters final in April in their most recent meeting.
"I will have to raise my game," said Djokovic, who lost the 2012 Paris final to Nadal.
"Nadal is in great form but the win in Monte Carlo has given me great confidence. I will be positive."
Wednesday's quarter-final proved a match too far for the 35-year-old Haas who was bidding to become the oldest semi-finalist at a major since Andre Agassi at the 2005 US Open.