Vinales became the first rider to win a Sunday race with three different manufacturers - having won with Suzuki and Yamaha in the past - taking the chequered flag in an eventful race that had several lead changes.
Red Bull GasGas Tech3's 19-year-old rookie Pedro Acosta took the lead on two different occasions but he finished second to become the youngest rider to take back-to-back podiums while Ducati's Enea Bastianini was third.
Championship leader Jorge Martin finished fourth to see his lead over Bastianini in the riders' standings cut down to 21 points while reigning champion Francesco Bagnaia was fifth.
Vinales carved his way from 11th to win and deny manufacturers Ducati a 12th consecutive race victory in MotoGP, with the Spaniard donning a black cape to go with the Batman logo on his helmet to celebrate his first race win since 2021.
"I was feeling everyone pushing me... It was spectacular. What can I say? History made. I'm dreaming," said Vinales, who is nicknamed 'BatMav'.
"I'm super happy... I don't know how many overtakes I did!"
Acosta took the lead when the lights went out while Martin stole four places as they emerged through yellow smoke from flares and dived into turn one, pushing Marc Marquez down to fourth while even Ducati's Bagnaia moved ahead.
After a couple of unsuccessful attempts, Martin finally found a way past Acosta three laps in using the power of his Ducati to take the lead while Marquez also capitalised on the same lap to slip past Bagnaia to move up to second.
RISKY OVERTAKE
Marquez had his heart in his mouth when a risky overtake manoeuvre with 15 laps left saw Martin clip his front wheel, pushing the Gresini rider down to fourth as he tried to regain his balance and composure.
But both Acosta and Marquez managed to overtake Bagnaia in quick succession to push the defending champion out of podium contention.
Although Marquez managed to take the lead at the halfway stage as he sought his eighth victory at the Circuit of the Americas and first with Gresini, the Spaniard crashed out of the lead to give Acosta clear air up front.
But Vinales confidently moved up the pack and he soon found himself involved in an intense battle for first place as he constantly swapped positions with Acosta before taking the lead outright, staying in front until the chequered flag.
Martin was denied a podium with two laps to go when Bastianini, who had hounded him in the final stages, eventually powered past the Spaniard.
Martin has 80 points after three rounds while Bastianini has 59. Vinales is third in the championship with 56 points while Acosta is two points further behind.
