Saturday's sprint winner Maverick Viñales dropped heavily in Austin early in the race, which rookie Acosta used to take the lead, fending off attacks from Martin and Bagnaia. As the race progressed, Acosta began to lose a little ground, allowing Martin, Marc Márquez and Bagnaia to pass him.

With eleven laps to go, Acosta regained the lead, closely followed by Marc Márquez and Martin. Viñales, despite his earlier setback, began to chase down the leaders with Bagnai in tow. Later, Marc Márquez took the lead, but only briefly. The Spanish rider crashed, opening the way for Viñales to take the top spot. Meanwhile, Bastianini made a decisive move to secure third place.

Viñales then held on to the lead and was able to celebrate his first triumph with Aprilia. The Spaniard also became the first rider to win a MotoGP Grand Prix on machines from three different brands.

Pedro Acosta finished second and became the youngest rider to win two consecutive titles in the premier class. Enea Bastianini took the third step of the podium. Jorge Martin finished fourth, but remains at the top of the championship