Marc Marquez cruised to his sixth successive Austin victory, ahead of Maverick Vinales, while Andrea Dovizioso took the lead in the standings with fifth.
Starting from fourth following a three-place grid drop for blocking Vinales in qualifying, Marquez eased ahead of Suzuki's Andrea Iannone at Turn 12 on the opening lap.
Iannone kept the Honda rider honest in the very early stages, and even mounted an assault on the Spaniard's lead at Turn 11 on the third lap.
However, Iannone ran wide on the exit of the corner and allowed Marquez to pounce straight back, with the Honda rider immediately putting two seconds between himself and the rest of the field.
Poleman Vinales reeled in Iannone by lap six, and scythed through to take second away from him at the start of the seventh tour.
Vinales quickly dropped the Suzuki rider, though he came under no threat from the chasing Valentino Rossi on the sister factory Yamaha.
Marquez remained settled to the chequered flag to claim his first win of the season, with Vinales and Iannone completing the top three, the latter taking his first podium as a factory Suzuki rider.
Rossi was a distant fourth in the end, while Dovizioso got the better of Tech3's Johann Zarco in the closing stages to take fifth and a slender one-point lead in the standings ahead of Marquez.
Dani Pedrosa gritted his teeth to claim seventh despite his wrist injury, while Avintia's Tito Rabat held Ducati stablemate Jack Miller and Aprilia's Aleix Espargaro at bay to secure eighth, while Jorge Lorenzo was cast a distant 11th.
Danilo Petrucci trailed Lorenzo home in 12th, with Pol Espargaro, Takaaki Nakagami and Alvaro Bautista taking the remaining points.
Championship leader prior to this race, Cal Crutchlow heads to the Spanish Grand Prix next month eight points down in fourth after crashing at the final corner on lap eight while battling for fifth with Zarco and Dovizioso.
The Briton remounted, but was unable to salvage any points in 19th. Alex Rins and Hafizh Syahrin crashed in the opening half of the race, while Karel Abraham was forced to retire due to pain in his wrist from his qualifying crash.
