The 27-year-old Italian, starting second on the grid, quickly grabbed the lead and never looked back for his second win of the year after his triumph at the season-opening Thailand Grand Prix earlier this month.
Jorge Martin made it an Aprilia 1-2, and VR46's Fabio Di Giannantonio held off Marc Marquez down the stretch to claim third.
Adjustments made
Bezzecchi said he and his team were forced to dig deep after struggling during Friday's rain-hit practice.
"It was a tough weekend, it was super tough on Friday, we started in a bad way, and it was difficult to keep the motivation super high," Bezzecchi said.
"But the guys did a wonderful job and I pushed myself over the limit to try to compensate for everything I could and at the end we found the way to make the bike in a fantastic way.
"I adjusted some details on my riding and from this morning I felt better, so I said, 'Okay, maybe I can try to fight.' It was an amazing race, I'm super happy."
With the win, Bezzecchi overtook KTM's Pedro Acosta and now leads the championship standings by 11 points.
Bezzecchi dedicated the victory to his friend Roberto Lunadei, a 42-year-old mechanic who died in a road traffic accident last week.
Track concerns
The race distance was cut from 31 laps to 23 amid track degradation concerns and scorching temperatures in Goiania, a change that was only announced just before the start of the race.
Saturday's sprint race was delayed by more than an hour as officials carried out urgent track repairs after a large hole was discovered near the starting line.
The competition at the Ayrton Senna Circuit marked MotoGP's return to Brazil for the first time in more than two decades.
MotoGP action now shifts from South America to North America with the US Grand Prix in Austin, Texas, on March 27th-29th.