Piastri arrived in Formula 2 for 2021 already carrying significant momentum. The Australian had won the 2019 Formula Renault Eurocup with R-ace GP, then secured the 2020 FIA Formula 3 Championship with Prema. He replaced Mick Schumacher at Prema for the Formula 2 campaign, partnering Ferrari Driver Academy member Robert Shwartzman. Before the season began, Piastri described his own expectations as modest, stating he anticipated "a very challenging year" and had originally planned to spend two seasons in the category before pushing for a Formula One seat.
Piastri began the year at Sakhir, qualifying seventh and finishing fifth in the opening sprint. His maiden Formula 2 victory came in the second sprint race at Sakhir, when he produced seven overtakes in the final seven laps after pitting for option tyres under a safety car and passing Zhou Guanyu on the last tour for the lead. The feature race ended with a collision retirement while battling for third with Dan Ticktum, a sharp reminder of the tight margins in the championship.
At Monaco and Baku, Piastri qualified third at both venues and collected second places in the sprint and feature races, steadily building his points tally. His maiden Formula 2 pole came at Silverstone, and a sequence of finishes — sixth, fourth, and third — gave him the championship lead from Zhou Guanyu entering the second half of the season.
The decisive mid-season stretch saw Piastri win the Monza feature race from pole in a direct fight with Zhou, then repeat the feat at Sochi with Théo Pourchaire as the closest pursuer. At Jeddah, he won both the second sprint race and the feature from pole, the latter result delayed by multiple red flags. The title was clinched at Yas Island during the first sprint race: starting tenth, Piastri came through to third in a late battle with his teammate Shwartzman — enough to seal the championship regardless of remaining results. He then closed the season with his fourth consecutive feature race victory, a record in itself.
Piastri finished on 252.5 points, 60.5 ahead of runner-up Shwartzman. Across the season he claimed six wins from eleven podiums, with five pole positions and five fastest laps. The margin and consistency were particularly striking given pre-season expectations about the steep learning curve of a first Formula 2 campaign.
The 2021 championship consolidated Piastri's status as one of the most efficient junior-formula climbers in recent memory. He became only the third driver in the GP3/Formula 3 and GP2/Formula 2 era to win both those titles in back-to-back seasons, following Charles Leclerc and George Russell. He was also the first driver to win Formula Renault, Formula 3, and Formula 2 equivalents in three consecutive seasons — a feat regarded at the time as historically unprecedented in junior single-seater racing. The FIA named him Rookie of the Year for 2021.
Despite the title, Piastri found no immediate Formula One seat for 2022, instead serving as Alpine's reserve driver. That situation led to the high-profile 2022 contract dispute with Alpine before he ultimately joined McLaren for 2023, making his Formula 2 title one of the most discussed cases of a champion waiting for a race seat.