Prema had won the 2020 teams' championship with Mick Schumacher and Robert Shwartzman, and Schumacher had taken the drivers' crown before graduating to Formula One with Haas. For 2021 Prema retained Shwartzman, who had finished fourth the previous year, and replaced Schumacher with Oscar Piastri, the reigning FIA Formula 3 champion. The 2021 season itself brought a structural overhaul: each of the eight rounds hosted three races instead of the previous two, a cost-cutting measure introduced in response to the COVID-19 pandemic that separated the Formula 2 and Formula 3 calendars onto alternating weekends.
The opening rounds showed the championship was anything but a Prema procession. At Bahrain, Piastri crashed out of the feature race on the final laps while running with the lead group, while early title favourite Guanyu Zhou of UNI-Virtuosi won and built a 16-point lead after Monaco. Shwartzman endured costly collisions at both Bahrain and Monaco before finding better pace. Through the Baku and Silverstone rounds the picture shifted: Zhou's campaign stalled with a spin and retirement at Silverstone that dropped him from the lead, leaving Piastri at the top of the standings.
From Italy onward, Piastri was dominant. He secured pole for five consecutive feature races — from Silverstone to the season finale at Yas Marina — and won each of those feature races, four of them consecutively. Shwartzman recovered to score consistently from Baku to Abu Dhabi, finishing in the top six in all but one race from that point on, and the combined points from the two Prema drivers gave the team the teams' title with a round to spare.
Piastri clinched the drivers' championship at Yas Marina by winning Race 1 at the season finale, wrapping up the title as a first-year driver — a rare achievement in the series. Shwartzman finished second in the championship. The Prema double sealed the teams' title for the Italian squad in back-to-back years, underscoring the team's grip on the FIA-regulated feeder ladder.
Piastri's 2021 campaign formed part of a larger development trajectory enabled by his place in the Alpine Driver Academy. Despite that association, Piastri did not receive a Formula One seat with Alpine for 2022 and instead spent that year as a reserve driver before signing with McLaren for 2023. His Formula 2 title was a key part of the record that eventually brought him to Formula One. Shwartzman, backed by the Ferrari Driver Academy, continued in Formula 2 for a third consecutive season in 2022.
Prema first entered the GP2 Series in 2016, finishing first and second with Pierre Gasly and Antonio Giovinazzi on debut. When the series rebranded as FIA Formula 2 in 2017, Prema won the inaugural drivers' title with Charles Leclerc and followed with further championships courtesy of Mick Schumacher in 2020 and Piastri in 2021. The 2021 result continued Prema's pattern of identifying and developing drivers who subsequently graduated to Formula One, with Piastri following Leclerc, Russell, and Schumacher in that path from the Prema Formula 2 programme.