Ducati has won the previous two Qatar GPs courtesy of Andrea Dovizioso, but Vinales finished that run after battling his way through the Desmosedicis after a slow start.
Police officer Francesco Bagnaia led a Ducati attack from the line as teammate Jack Miller, Pramacs Johann Zarco and his rookie teammate Jorge Martin flashed the Yamahas from 14th on the grid at Turn 1.
Martin and Zarco finished in third place, the Frenchman holding onto Turn 6 while the pre-race favorite, Franco Morbidelli, dropped from seventh on the grid to 20th.
The Yamaha trio of Vinales, Fabio Quartararo and Valentino Rossi from SRT regrouped later in the first round, with Quartararo bringing them back to fifth place.
The Frenchman would lead Martin in turn 6 on lap three, while Vinales followed him on turn 10.
Bagnaia’s lead over Zarco was seven tenths, while Quartararo’s deficit at Turn 15 remained ahead of Miller at Turn 15 and the Ducati rider’s door closed on the way into Turn 1.
Vinales would follow his teammate two tours later, with the Spaniard finishing third from Quartararo on lap 11.
There was nothing Zarco could do to stop Vinales’ attack a lap later at Turn 10. The strong headwind on Sunday prevented the Ducatis from using their performance advantage over the others.
Vinales launched an attack on Bagnaia’s lead on lap 14 on lap 10, but the Ducati didn’t give in and the pair got close to contact as they ran side by side through Turn 11.
The Yamaha rider did the job in the same location a lap later and immediately pulled out a lead of over half a second when the Ducati riders encountered grip problems.
Vinales’ attack at the front was relentless, with a 1.6 second lead when he started the penultimate lap.
On the final lap, he was under no threat to claim his ninth MotoGP win of his career and take the lead early in the championship.
Suzukis Mir came through from tenth on the grid and took second place in turn 15 on the last lap.
But the world champion ran far in the last corner, leaving both Zarco and Bagnaia on the way to the checkered flag to demote him to fourth place.
Quartararo made a late rally after declining orders to finish his first race as a factory Yamaha rider in fifth place. Alex Rins’ podium finish on the second Suzuki eventually ended in sixth place.
Aleix Espargaro was seventh on the Aprilia ahead of his brother Pol on his Honda factory debut, while Miller on the Avintia Ducati was ninth in front of top rookie Enea Bastianini.
On his SRT debut, Rossi couldn’t convert a strong fourth place in qualifying to his 200th MotoGP podium. The nine-time Grand Prix World Champion was an average of 12th behind Honda’s Stefan Bradl.
Miguel Oliveira led KTM team-mate Brad Binder in 13th place, while Martin fell back to 15th place after his quick start to the race.
Morbidelli’s problems persisted throughout the race. The runner-up in the 2020 championship took the checkered flag in 18th place behind Avintia rookie Luca Marini and Iker Lecuona from Tech 3, but ahead of Lorenzo Savadori from Aprilia.
Tech 3’s Danilo Petrucci crashed on the first lap, and LCR duo Takaaki Nakagami and Alex Marquez came to the sidelines through separate falls.