The RB16 was planned to make its competitive debut at the 2020 Australian Grand Prix, but this was delayed when the race was cancelled and the next three events in Bahrain, Vietnam and China were postponed in response to the COVID-19 pandemic.

Under an agreement between teams and the Fédération Internationale de l'Automobile, 2020-specification cars—including the RB16—saw their lifespan extended to compete in 2021, with Red Bull producing an updated chassis called the RB16B, which used Honda's upgraded RA621H power unit.

[15] Due to difficulties caused by the COVID-19 pandemic, Honda had initially decided to postpone the introduction of its all-new power unit design to the 2022 season.

[16] Some features of the RA621H include a notably more compact camshaft layout that is placed lower, a different valve angle and shorter cylinder bore spacing compared to the previous season's RA620H.

[19] Verstappen and Albon started second and fourth on the grid respectively for the season-opening Austrian Grand Prix, however both cars would go on to retire with electrical failures during the race.

The team ended the year on a high, with Verstappen scoring a dominant victory in Abu Dhabi, the first time Red Bull won at the circuit since 2013.

Verstappen fought for the championship with Lewis Hamilton all season long,[26] winning it on the last lap of the Abu Dhabi Grand Prix, after a last-minute restart, caused by a crash from Nicholas Latifi.