Morbidelli's father Livio was a former motorcycle racer who competed in Italian national championships but lacked the resources to fund his son's career. Through a contact with Graziano Rossi — father of nine-time world champion Valentino Rossi — the family sold their home in Rome and relocated to Tavullia, the racing enclave in central Italy that became the cradle of the VR46 Academy. Morbidelli became the academy's first official member. In January 2013, his father died by suicide.
Before entering Grand Prix motorcycle racing, Morbidelli spent three seasons in the FIM European Superstock 600 Championship, winning the title in 2013 aboard a Kawasaki with Team Italia. That success earned him wild-card entries with Gresini in the 2013 Moto2 championship, though he did not score points across three appearances.
He joined the Moto2 class full-time in 2014 with the Italtrans Racing Team, outscoring more experienced teammate Julián Simón. He secured his first podium — a third at the Indianapolis Grand Prix — in 2015.
After joining the Marc VDS Racing Team in 2016 alongside Álex Márquez and recording eight podiums, Morbidelli arrived at the 2017 season as a title favourite. He validated that billing immediately, winning the opening round in Qatar and going on to claim eight race victories across the year. He clinched the 2017 Moto2 World Championship at the Malaysian Grand Prix after closest rival Thomas Lüthi was declared unfit to race following a qualifying crash. Morbidelli finished the season with eight wins and four additional podiums.
Morbidelli stepped up to MotoGP in 2018 with Marc VDS on a 2017-specification Honda RC213V, finishing 15th in the standings and winning the Rookie of the Year award. When Marc VDS departed the premier class, he moved to the newly formed Petronas Yamaha SRT team for 2019 on a two-year deal, finishing tenth in his debut season.
The 2020 season proved to be his finest in MotoGP. Riding a 2019-specification Yamaha — one year behind the machinery his teammate Fabio Quartararo received — Morbidelli delivered a series of outstanding performances. He took his first premier-class victory at the Rimini round and added a second win at the Teruel Grand Prix, setting a new lap record. He claimed a third victory at the second Valencia round and ultimately finished the shortened season as runner-up to Joan Mir by just 13 points, a remarkable achievement given the equipment disparity.
After a knee injury sustained in a training accident disrupted his 2021 campaign, Morbidelli was promoted mid-season to the factory Yamaha Motor Racing squad to fill the seat vacated when Maverick Viñales was dismissed by the team.
Morbidelli remained at the Monster Energy Yamaha factory team through 2022 and 2023, partnering reigning world champion Fabio Quartararo, but results were modest as Yamaha struggled with competitiveness against the dominant Ducati platform. He moved to Prima Pramac Racing on a Ducati for 2024, finishing ninth in the championship and recording his first sprint race podium at the San Marino Grand Prix.
For 2025 and 2026, Morbidelli returned full circle to the VR46 Racing Team — the organisation founded by his long-time mentor Valentino Rossi — partnering Fabio Di Giannantonio on a Ducati Desmosedici GP24.
Morbidelli's 2020 MotoGP season — runner-up on satellite machinery — stands as one of the most impressive underdog campaigns in modern premier-class history. As the first graduate of the VR46 Academy to win a world championship and reach the MotoGP factory ranks, he remains one of the most significant figures produced by Rossi's talent development programme.