Bezzecchi had delivered a commanding lights-to-flag victory at the Portuguese Grand Prix last weekend and the Italian repeated his heroics in Valencia, celebrating by getting down on one knee and proposing to his beloved bike.
Raul Fernandez of Trackhouse finished second to give Aprilia a one-two finish while Fabio Di Giannantonio of VR46 Racing stole third from KTM's Pedro Acosta at the end to ensure a Ducati bike finished on the podium once again.
The Circuit Ricardo Tormo was hosting a MotoGP race for the first time since 2023 after last year's season finale was moved due to catastrophic floods in the region that killed more than 200 people.
"I had a lot of fun, I have to be honest, especially in the end because Raul was super fast, super close and always getting closer lap by lap. So it was tough," Bezzecchi said moments after crowd-surfing on Aprilia's mechanics.
"But very, very happy super satisfied about the job from the guys. I can't hope for a better way to finish the season and now we are going to celebrate for sure. But Tuesday, we start (testing for) 2026."
Warm-up lap drama
There was drama at the end of the warm-up lap when Franco Morbidelli was forced to retire before the start of the race after he lost concentration and collided with Aleix Espargaro on the grid, fracturing his left hand as he fell over.
When the lights went out, polesitter Bezzecchi had a superb launch to take the lead into turn one ahead of sprint winner Alex Marquez while Di Giannantonio was in third.
Ducati rider Francesco Bagnaia's miserable season came to an end on the opening lap after just four turns when he suffered a crash following a collision with Johann Zarco.
Bagnaia was once in the running for a top-three finish in the standings at the start of the year but the twice-champion finished fifth - 257 points behind champion Marc Marquez - after ending the season with five consecutive retirements.
Fernandez then found his way up to third and on lap 12 he dived inside Alex to move up to second and set his sights on Bezzecchi.
Martin withdrawn as a precaution
Last year's champion Jorge Martin, who was returning to the track after an injury-plagued season and running last, pulled into the pits as Aprilia decided to withdraw him from the race after 15 laps as a precaution.
Alex, meanwhile, was struggling for pace and Acosta, who had been closing in on the Gresini Racing rider, pounced on lap 20 as he moved clear of his compatriot to slot into third place.
On the next lap, Di Giannantonio also made his move to overtake Marquez, who was not willing to take any risks having sealed his runner-up spot in the championship in Malaysia last month.
That gave Di Giannantonio the opportunity to attack Acosta and with two laps left, the Italian cut inside to take third from the young KTM rider before keeping him at bay to keep Ducati's 88-race podium streak intact.
"After half the race I got my rhythm again, I saved the tyres and I was able to be faster at the end. The fight for third place was amazing," he said.