The W12 was based on its predecessor, the Mercedes-AMG F1 W11 EQ Performance, which had won the Drivers' and Constructors' Championships in 2020. Regulation changes for 2021 reduced downforce generated by the floor area; commentators Lawrence Barretto, Scott Mitchell, Mark Hughes, and Edd Straw judged that these changes compromised lower-rake designs such as the W12 more than higher-rake designs such as the Red Bull RB16B. The banning of the Dual Axis Steering (DAS) system, previously a Mercedes feature, was a further constraint. Those same pundits made Red Bull favourites for the opening round following stronger performance in pre-season testing. Williams driver and Mercedes protégé George Russell, who had driven the W11 at the 2020 Sakhir Grand Prix, also noted that both the W12 and the Williams FW43B could have issues with wind sensitivity.
Max Verstappen took pole at the Bahrain Grand Prix season opener, but Hamilton won the race after Mercedes undercut Verstappen by pitting Hamilton for hard tyres at the end of lap 14. At the Emilia Romagna Grand Prix, Hamilton took his 99th pole but went off-track into the gravel on lap 31, rejoined eighth, and finished second more than 20 seconds behind Verstappen following a red-flag restart. Bottas retired after a collision with Russell. At the Portuguese Grand Prix, Bottas took pole; Hamilton won by over 29 seconds from Verstappen. Hamilton claimed his 100th pole at the Spanish Grand Prix and won after overtaking Verstappen on lap 59.
At the Monaco Grand Prix, Hamilton qualified seventh following tyre temperature problems — his worst qualifying result since the 2018 German Grand Prix — and finished seventh while Bottas retired when the team failed to remove a wheel during a pit stop. At the Azerbaijan Grand Prix, both Mercedes drivers failed to score points for the first time since the 2012 United States Grand Prix; Hamilton locked up into turn 1 at the second restart having selected the wrong brake mode. At the French Grand Prix, Verstappen undercut Hamilton and won by three seconds, with Bottas finishing fourth.
The Styrian and Austrian Grands Prix were dominated by Verstappen, who achieved his first grand slam at the Styrian round; he took both wins while Hamilton finished second at Styria and Bottas second at Austria. Verstappen extended his championship lead by 32 points across those two races. Mercedes introduced a major upgrade package for the British Grand Prix. Hamilton won after a controversial opening-lap collision at Copse corner with Verstappen, who hit the barrier; Hamilton was judged predominantly but not fully at fault and was given a ten-second time penalty. This was Hamilton's record-equalling eighth British Grand Prix win. At the Hungarian Grand Prix, Hamilton was the only driver on the grid at the second restart (the rest having pitted for slick tyres); he worked up to third before Sebastian Vettel's post-race disqualification promoted him to second, allowing Mercedes to take the championship lead from Red Bull.
At the Belgian Grand Prix, heavy rain caused a three-hour delay and only three laps were run behind the safety car; it became the shortest race in Formula One history and the sixth to award half-points. Verstappen won by countback, Russell scored his first F1 podium in second, and Hamilton was classified third. Hamilton's championship lead was cut to three points. At the Dutch Grand Prix, Hamilton qualified 0.038 seconds behind Verstappen, set the fastest lap, and finished second; Bottas was third. At the Italian Grand Prix, Hamilton started fourth (Bottas was relegated to the back for exceeding power unit component limits despite qualifying on pole for the sprint). Hamilton and Verstappen collided on lap 24; both retired and Hamilton recorded his first retirement since the 2018 Austrian Grand Prix. Bottas finished third.
At the Russian Grand Prix, Hamilton qualified fourth after contact with the pit wall in Q3 damaged his front wing and prevented tyre warm-up. Rain on lap 48 prompted Hamilton to pit for intermediates; race leader Lando Norris stayed on slicks, ran wide on lap 51, and Hamilton inherited the lead to take his 100th Formula One victory. At the Turkish Grand Prix, Hamilton qualified fastest but was dropped down the grid by a power unit penalty; Bottas started from pole and took his first win of the season while Hamilton finished fifth. At the United States Grand Prix, Hamilton took the lead at turn 1 but lost it after pit stops and finished second, 1.3 seconds behind Verstappen. At the Mexico City Grand Prix, Bottas was on pole but Daniel Ricciardo tagged him at turn 1; Hamilton finished second behind Verstappen.
At the São Paulo Grand Prix, Hamilton qualified on pole but was disqualified because his car's DRS opening slot measured wider than the permitted 85 millimetres; he started the sprint from the back and recovered to fifth from 24 laps. For the race, Hamilton took a new engine and started tenth; he fought to the front and on lap 59 passed Verstappen — who had pushed him wide on lap 48 without stewards taking action — to win. At the Qatar Grand Prix, Hamilton took pole and led every lap, winning 25 seconds ahead of Verstappen.
At the inaugural Saudi Arabian Grand Prix, Hamilton took pole and won, also setting the fastest lap, after a series of incidents involving Verstappen — including a brake test by Verstappen for which the stewards gave Verstappen a ten-second penalty and then an illegal re-pass for which no penalty was applied. Both drivers entered the Abu Dhabi Grand Prix level on points. Hamilton led and built an 11-second gap before Sergio Pérez held him up, allowing Verstappen to close. A safety car on lap 53 following Nicholas Latifi's crash gave Verstappen the opportunity to pit for fresh soft tyres. Race director Michael Masi allowed only the lapped cars between Hamilton and Verstappen to unlap themselves, restarting the race for a single final lap. Verstappen overtook Hamilton at turn 5 and won the Drivers' Championship; Hamilton crossed the line second. Bottas finished third in the championship. Mercedes won their eighth consecutive Constructors' Championship, a new record.
Following its competitive season, the W12 was used at the opening of the Las Vegas Grand Prix street circuit (wearing the 2022 W13 livery), at the 2023 Goodwood Festival of Speed (wearing the 2023 W14 livery), and in April 2024 on Fifth Avenue in New York ahead of the Miami Grand Prix (wearing the 2024 W15 livery). In April 2026, Mercedes development driver and 2025 F1 Academy champion Doriane Pin drove the car for 76 laps in a private test at Silverstone Circuit.
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