The 6-2, 6-3, 6-1 win over the Swiss brought the Spaniard's match record at Roland Garros to a remarkable 57-1 as he seeks to become the first player in history to win the same grand slam title eight times.
But to get to Sunday's final, he will have to defeat top seed and great rival Djokovic, who won their last encounter on clay in Monte Carlo in April, in a semi-final match on Friday.
Djokovic had a slightly harder time of it against German veteran Tommy Haas, advancing on a 6-3, 7-6, 7-5 score line.
"I think today I played my best match of this year at the tournament. I was very happy with the conditions on a court that is so emotional for me," said Nadal
"Stan was a little bit tired after his incredible match against Richard [Gasquet] which I thought was the best match of the tournament so far."
The odds were firmly stacked against Wawrinka going into what was his first French Open quarter-final match in nine attempts.
He had lost all nine previous matches against Nadal, failing to win a single set, and had needed treatment for a leg strain during his five-set marathon win over Gasquet in the fourth round when he came back from two sets down.
Nadal broke the Swiss player's serve in the opening game and then again in the fifth to take the first set 6-2.
Nadal then jumped out into a 3-1 lead with another break early in the second set before Wawrinka had a glimmer of hope with a break back to get to 3-3.
But that was as far as it got for the ninth seed.
Nadal simply added extra muscle to his pounding groundstrokes, leaving Wawrinka reeling under their weight and precision.
Nadal ran off three games in a row to take a two sets to love lead and it was clear that Wawrinka's chances of another major comeback were next to impossible.
To make matters even worse, Wawrinka needed further treatment to his strained thigh even before the third set could get underway.
He did have a break point to savour as the third set got underway, but a thumping Nadal first serve erased that and then Wawrinka was broken again in the next game. Nadal was now in full flow and Wawrinka's shoulders started to slump as he stumbled on towards inevitable defeat.
A disappointed centre court crowd tried to instil some belief into the Swiss player, but he was beyond help as Nadal ran off the four games he needed to book his place in the semi-finals.
Next up for Nadal is the Djokovic, who needs a Roland Garros title to become just the eighth man to complete a career Grand Slam.
"I will have to raise my game for the next match," said the Serbian.
"Nadal is in great form but the win in Monte Carlo has given me great confidence.
"I will be positive."
It was a match too far for the 35-year-old Haas who was bidding to become the oldest semi-finalist at a grand slam since Andre Agassi at the 2005 US Open and second oldest in Paris.
MARIA SHARAPOVA SURVIVES TO REACH SEMI-FINALS
Sharapova, the defending champion, seeded second this year, survived a nightmare start to hold on to her crown for at least another day with a 0-6, 6-4, 6-3 win over Jelena Jankovic in a compelling last-eight tie.
World No 3 Azarenka, meanwhile, reached her first semi-final at Roland Garros when she defeated friend and former doubles partner, Maria Kirilenko of Russia, 7-6, 6-2.
Sharapova and Azarenka have played each other 12 times with the Belarusian 7-5 ahead, although it will be their first meeting this year.
The 26-year-old Russian Sharapova was all over the place for a set and 30 minutes in her match against Jankovic, but with the exit door beckoning, she steadied her nerves enough to apply the firepower needed to derail the Serb's challenge.
"She played such a great match from the beginning and was very aggressive," Sharapova said of her opponent.
"I knew after the first set that I had to change things around. I just had to erase the chapter and move forward. I still felt I was in the match and I broke her in the first game [of the second].
It was just the fourth time in her grand slam career that Sharapova had lost a set 6-0, but she could have no complaints, having committed 20 unforced errors to just two from Jankovic.
Australian Open winner Azarenka needed 76 minutes to claim a marathon first set but once 23 year old had pocketed that, it was clear that Kirilenko, who needed a medical timeout after the seventh game, simply lacked the armoury to upset her bigger and stronger opponent
The women's semi-finals will be held with top seed Serena Williams taking on last year's runner-up Sara Errani in the other match.
Follow us @SprtNationalUAE