The RB21 marked a notable transition in Red Bull's technical structure. It was the first Red Bull Racing car since the RB2 not to be designed by former Chief Technical Officer Adrian Newey, and the first car to be designed and overseen in production by Technical Director Pierre Waché. The car was powered by the Honda RBPTH003 power unit and represented the final season of Red Bull Racing's association with Honda RBPT-badged engines; from 2026 the team and its sister outfit Racing Bulls would switch to Red Bull Powertrains engines developed with Ford, while Honda moved to power Aston Martin. Two mid-season upgrade packages were introduced during the year, the first at the Miami Grand Prix and the second at Monza.
Pre-season testing at Bahrain International Circuit covered 304 laps — the fewest of the ten teams — and both Verstappen and Lawson flagged concerns ahead of the opening round. McLaren's MCL39 set the early pace, and Lawson struggled badly, enduring two last-place qualifying efforts at the Chinese Grand Prix weekend before Red Bull moved to replace him with Tsunoda from the Japanese round onward. Verstappen opened his account with a podium in Australia and victories at the Japanese and Emilia Romagna Grands Prix. The team marked their 400th Grand Prix at Imola by running retro-style car numbers evoking the 2005–2013 livery era, while the Japanese round featured a special matte white "White Bull" tribute honouring the final year of the Honda partnership.
The mid-season period proved difficult. Tsunoda's heavy qualifying crash at Imola left him without upgrades for several subsequent rounds. At the Austrian Grand Prix, a lap-one collision with Kimi Antonelli's Mercedes eliminated Verstappen, leaving Red Bull without points at their home race for the first time since the 2022 Bahrain Grand Prix. Persistent handling and tyre-degradation weaknesses were exposed at the British Grand Prix, where Verstappen spun at Stowe while on quickly overheating intermediates and dropped to fifth. A disastrous São Paulo qualifying produced Red Bull's first Q1 exit since 2006. By the time Verstappen won in Azerbaijan for his fourth victory of the season, the team had already been eliminated from the Constructors' Championship fight.
Verstappen's Drivers' title bid revived across the final flyaway rounds. He won in the United States, Las Vegas, Qatar, and Abu Dhabi — four victories in the closing stretch — and went to the finale with a realistic chance at the championship. Winning the Abu Dhabi Grand Prix from pole position, he was nonetheless outscored overall by Lando Norris, who finished second and claimed his first Drivers' title by two points. Tsunoda's contribution was modest throughout; his best result was a sixth place in Azerbaijan.
The car's livery was revealed at the F1 75 event at The O2 Arena on 18 February 2025, broadly following previous Red Bull designs with minor sponsorship adjustments. The Japanese Grand Prix variant — matte white with satin red logos in the national racing colours of Japan — was the most distinctive appearance of the season.
Following the Abu Dhabi finale, the RB21 remained at Yas Marina Circuit for post-season testing focused on the incoming 2026 regulations. With both Verstappen and Tsunoda absent, Red Bull fielded Isack Hadjar in a mule car adapted to simulate 2026 aerodynamic conditions for tyre development work with sole supplier Pirelli, while Ayumu Iwasa drove the standard-specification car.