On 22 January 2021 Dorna announced a significant update of the provisional calendar following the postponement of the Argentine and American Grands Prix, originally scheduled as the second and third rounds of the championship (on 11 and 18 April respectively) due to the COVID-19 situation in both countries, with potential rescheduling for the last quarter of 2021.

On the same day Dorna announced an agreement with the organizers of the Portuguese Grand Prix to hold the race on the Algarve circuit as the third stage of the 2021 championship (the first of the season in Europe) on 18 April.

Raúl Fernández is third with 26 points, one more than Marco Bezzecchi and five more than Fabio Di Giannantonio.

Marc Márquez returns as Honda's starter rider after the incident in the 2020 Spanish Grand Prix, which is valid as the first race of the 2020 championship.

In the third session, Quartararo finished at the top of the standings ahead of Franco Morbidelli and Bagnaia.