Red Bull KTM's Brad Binder had finished third but just as in the sprint, his podium was snatched away from him for a second time when he was demoted for exceeding track limits, handing third place to Aprilia's Aleix Espargaro.
With the track outline tattooed onto his arm, Bagnaia probably knows the 'Cathedral of Speed' better than most and he did not put a foot wrong in hot conditions to take the chequered flag for his fourth race win of the season.
Bagnaia moved up to 194 points in the standings and leads Jorge Martin by 35 points while Bezzecchi is a further point behind.
"It's fantastic, it wasn't easy... I just managed to open a gap in the last laps, I was quite on the limit. I love this track," Bagnaia said after claiming back-to-back wins in Assen.
Red Bull KTMs have been the fastest off the line this season and Binder had a sensational start, using his bike's launch control to move up from fifth to first by turn one while Bezzecchi dropped to third behind Bagnaia.
Binder's teammate Jack Miller also moved up five places from 12th to seventh but he crashed out on the opening lap while Aprilia's Maverick Vinales lost his balance on a turn just after setting a fastest lap.
Yamaha's Fabio Quartararo was a surprise podium finisher in Saturday's sprint when Binder received the penalty but there was no such luck in the race as he crashed and also took out compatriot Johann Zarco and had to be helped off the track.
FASTEST LAPS
Up front, Bagnaia managed to get past Binder as the duo and Bezzecchi battled it out for the three podium spots, trading fastest laps as they extended the gap to the rest of the pack.
With 10 laps to go, Bezzecchi launched his attack when Binder was struggling with his rear tyre and the Italian timed his move to perfection to surge ahead and set his sights on Bagnaia but could not catch up with his compatriot.
Behind them, Binder seemed to have put Saturday's disappointment behind him but lightning struck twice as he strayed on the wrong side of the kerb by inches to give Espargaro the final podium spot.
Espargaro started sixth on the grid and had done well to move up after contact on the first lap which damaged the aero package on his bike and the Spaniard admitted he was finding it difficult to wrest control at times.
"I had contact with Luca Marini, I tried to avoid him... It wasn't easy to overtake Brad but I looked to stay behind him and it finally paid off," a grinning Espargaro said.
Honda's horror weekend after Marc Marquez withdrew before the race due to injuries only got worse as replacement rider Iker Lecuona was forced to retire with a mechanical problem.
