The 24-year-old broke his own world record in the near perfect performance on Thursday.
After making a loose start with his legs splayed apart as he dove into the pool, le Clos powered into the lead and stayed out in front with brilliantly executed turns before finishing the race in a record 48.08 seconds.
Le Clos had set a world record in 2014 at the World Championships in Doha, Qatar.
He won the race ahead of American Tom Shields took the silver in 49.04, and Australia’s David Morgan who settled for bronze in 49.31.
In victory, Le Clos joined Sweden’s Lars Frolander, the 2000 Olympic champion, in the club of triple winners of the 100m s/c crown. Frolander claimed his wins in 1997, 1999 and 2000, while Le Clos took his first title in 2012, retained it in 2014 and defended it on Thursday.