Marini made a wildcard Moto3 World Championship debut in 2013 at the San Marino Grand Prix before another wildcard entry in Moto2 in 2015 with Pons Racing. He joined Forward Team for a full-time Moto2 campaign in 2016, earning his first Grand Prix points in Qatar with a 10th place finish. His best result that year was sixth in Germany.
He improved steadily, joining the Sky Racing Team VR46 — the team co-owned by his half-brother Valentino Rossi — in 2018. That year brought his first Moto2 podium in Germany and first victory in Malaysia. In 2019 he added back-to-back wins in Thailand and Japan alongside podiums in Mugello and Assen.
The 2020 season was Marini's finest in the intermediate class. He won three races — in Spain, Misano, and Catalunya — and was involved in a three-way title battle with Enea Bastianini and Sam Lowes. The championship was ultimately decided in Bastianini's favour, but Marini secured second place on countback over Lowes — the two riders finished the season with identical points totals, with Marini placed ahead by virtue of a better finishing position in the final race in Portugal.
Marini moved to MotoGP in 2021 with the Esponsorama Avintia team, running under the Sky VR46 livery alongside Moto2 champion Enea Bastianini. His rookie season was one of adaptation, with consistent points-scoring finishes but no dramatic breakthroughs as he learned the demands of the Ducati Desmosedici in the premier class.
For 2022, Marini remained in the Ducati family with the newly formed Mooney VR46 Racing Team, partnering Marco Bezzecchi. He developed steadily with the satellite Ducati, and in 2023 delivered his breakthrough premier class results. He took his first MotoGP podium at Austin, claimed his first MotoGP pole position at the Indonesian Grand Prix, and had a standout weekend at the Qatar Grand Prix with pole and third-place finishes in both the sprint and the feature race. He ended the 2023 season eighth in the championship.
Despite initially extending with VR46, Marini was linked to the Repsol Honda seat vacated by Marc Marquez's departure, and Honda confirmed the signing shortly after the VR46 team announced his exit. The move to Honda represented a significant challenge, as the RC213V had become the least competitive machine among the top manufacturers.
The 2025 season was disrupted by a serious injury sustained during Suzuka 8 Hours testing on 28 May 2025. Marini suffered a dislocated left hip, ligament damage to the left knee, fractures of the sternum and left collarbone, and a pneumothorax, keeping him sidelined for three races. On his return at the German Grand Prix he finished a remarkable sixth. His best weekend of the season came at the Hungarian Grand Prix, where he qualified fourth in the sprint before finishing fifth in the feature race. Marini continued with Honda for the 2026 season alongside Joan Mir.
Marini is the son of Stefania Palma and Graziano Rossi, making him the maternal half-brother of Valentino Rossi. He grew up in the same motorsport environment as Rossi and developed through the VR46 Academy structure. The VR46 Racing Team that fielded him in MotoGP was co-founded by his half-brother.