Mir competed in the Red Bull MotoGP Rookies Cup in 2013 and 2014, winning three races and finishing runner-up to Jorge Martín in 2014. He contested the FIM CEV Moto3 Junior World Championship in 2015, winning four of the first six races before fading to fourth overall.
Mir made his Grand Prix debut in 2015 with Leopard Racing as a replacement at Phillip Island. He joined the team full-time for 2016, claiming his first Grand Prix pole and victory in just his eleventh start at the Austrian round, and finishing fifth overall as rookie of the year.
In 2017 he dominated the class, taking ten wins and 13 podiums from 18 races and clinching the title by 93 points over Romano Fenati.
Mir moved to Moto2 for 2018 with Marc VDS Racing Team, finishing the season sixth overall with four podiums and winning the rookie of the year award.
Mir joined Suzuki's factory MotoGP team for 2019, replacing Andrea Iannone. His rookie season was marked by consistent top-ten finishes — interrupted by two missed rounds following a pulmonary contusion — and a best result of fifth in Australia.
The 2020 season brought the world title. Despite not winning a race until the tenth round, Mir was remarkably consistent across a condensed, pandemic-affected calendar. He accumulated podiums in five of seven mid-season rounds while his rivals — Fabio Quartararo and Maverick Viñales primarily — dropped points. At the European Grand Prix at Circuit Ricardo Tormo, Mir took his maiden premier-class win, beating teammate Álex Rins. The following week, a seventh-place finish was enough to seal the championship as Quartararo crashed out, giving Mir a commanding total that could not be overhauled. The title was Suzuki's first in the premier class since Kenny Roberts Jr. in 2000 and the first by a non-Honda or non-Yamaha rider since Casey Stoner on Ducati in 2007. It also made Mir the first Moto3 world champion to go on to win the premier class title.
The 2021 season saw Mir finish third in the championship with 208 points, collecting podiums throughout the year. The 2022 campaign was disrupted by injury, leaving him 15th with 87 points.
Following Suzuki's unexpected withdrawal from MotoGP at the end of 2022, Mir signed with Repsol Honda, partnering Marc Márquez. The Honda RC213V struggled throughout 2023 and Mir ended the year 22nd, with fifth place at the Indian Grand Prix his best result.
After Márquez's departure to Ducati, Mir continued at Honda alongside Luca Marini for 2024 and 2025. Both seasons were marked by an uncompetitive machine and frequent crashes. In May 2026 Mir announced he would leave Honda at the end of the 2026 season.
Mir's 2020 championship is unusual in its consistency-over-speed character: he won only once in fourteen races yet controlled the standings through attrition and race-craft, a model of points-management that distinguished him from more aggressive title contenders. His parallel Moto3 and MotoGP titles placed him in an exclusive group of riders who won world championships in multiple Grand Prix classes.