He becomes the first man or woman in the Open era to have won a Grand Slam tournament 10 times. And for Wawrinka was beaten in a major final for the first time after winning his first three.
Nadal moves above Pete Sampras on the list of all-time Grand Slam winners into second place behind Roger Federer, who beat the Spaniard to win his 18th at the Australian Open in January.
Only Australia's Margaret Court has more victories at a single Grand Slam tournament, with 11 Australian Open wins between 1960 and 1973. Securing a 10th title in Paris - La Decima - further entrenches Nadal's place as the greatest clay-courter in history.
The Spaniard won the title for the loss of just 35 games over the course of seven matches, second only to six-time champion Bjorn Borg's 32 at the 1978 French Open.
He extended his record at Roland Garros to 79 wins and two losses since his first victory in 2005, the only defeats coming against Robin Soderling in 2009 and Novak Djokovic in 2014.
Martina Navratilova won Wimbledon nine times, while Roger Federer and Pete Sampras are the only post-war players among a group of six men to have won a Grand Slam seven times.