Pramac Ducati's Johann Zarco finished second with a stunning ride in the second half of the race while pole-sitter Alex Marquez was third on his Gresini Ducati for his first podium since the Aragon Grand Prix in 2020.
Reigning champion Francesco Bagnaia threw away 20 points when he made a mistake and crashed while he was in second place with eight laps left, conceding top spot in the championship to Bezzecchi - who now leads by nine points.
"I have no words because today, honestly, I woke up with a strange sensation. I knew I could go fast, but I didn't expect to go so fast," Bezzecchi said in a post-race interview.
"I was really scared of the wet because normally I'm not very good with the MotoGP (bike) on the wet but today it was fantastic. I had an incredible feeling since the first metre of the warm-up and I just enjoyed a lot with my bike.
"I was speaking to the bike just to stay concentrated and it was really, really tough. But it's an incredible feeling."
Marquez had overcome a crash and fire on his bike to clinch his maiden MotoGP pole on Saturday but Bezzecchi surged ahead at the start to take the lead at the first corner where he found better grip.
Once Bezzecchi had a clear track in front of him, the 2022 rookie of the year did not look back and extended his lead to three seconds with 15 laps to go while Marquez battled with Ducati's Bagnaia for second place.
Bagnaia eventually found a way past Marquez but soon after he made a mistake on turn 13 and slid off the track. Although he managed to finish the race, he crossed the line 16th and he was absolutely livid with himself.
Brad Binder shocked the grid when he won the sprint from 15th place but there would be no repeat of his opening lap heroics after he was clipped by Maverick Vinales and suffered a spill, rejoining the race but finishing dead last.
The two Aprilias of Vinales and Aleix Espargaro had dominated practice sessions on Friday but they were the slowest bikes on the track as they struggled in wet conditions, eventually finishing 12th and 15th.
Five riders did not start the race due to injuries, including both Hondas after Joan Mir was declared unfit.
