In his debut race, Mazepin crashed out on the first lap by losing control on the kerb at turn three. During the 2021 Portuguese Grand Prix, Mazepin was penalised 5 seconds for ignoring blue flags and blocking Sergio Pérez. At the 2021 Belgian Grand Prix in Spa-Francorchamps, which only lasted two laps behind the Safety Car due to heavy rain, Mazepin recorded the fastest lap of the race on the second lap; however, as the race was suspended permanently thereafter, the official results were taken from the end of the race's first full lap, and as a consequence, Mazepin's fastest lap award was rescinded.