Valentino Rossi founded the team in 2014 under the banner Sky Racing Team VR46, entering the Moto3 World Championship with the explicit goal of countering the dominance of Spanish riders that had characterized Grand Prix racing in the preceding decade. Romano Fenati and Francesco Bagnaia were the team's inaugural riders, with Rossi's former Cagiva teammate Vittoriano Guareschi serving as team manager. Fenati delivered four race wins in the debut season, finishing fifth in the championship; Bagnaia contributed 50 points despite missing rounds due to injury.
Pablo Nieto replaced Guareschi as team manager for 2015, a role he retained through the team's subsequent growth. Andrea Migno joined to partner Fenati, though neither rider challenged for the title. Romano Fenati was dismissed during the 2016 season due to a disciplinary dispute with the team management, and his place was taken by Lorenzo Dalla Porta. Nicolò Bulega, added as a third rider in 2016, showed junior-class potential before also departing. By 2019, Celestino Vietti and Dennis Foggia were the team's regular Moto3 riders, with Vietti achieving three podiums that season. VR46 departed the Moto3 class after 2020.
The team extended into Moto2 in 2017, selecting Bagnaia and Stefano Manzi as riders. Bagnaia proved immediately competitive, collecting four podiums in his rookie Moto2 season and finishing fifth overall. He won the Moto2 World Championship in 2018 with eight race victories — the team's first riders' title — with teammate Luca Marini also taking a race win that season. The following year Marini and Nicolò Bulega represented the team, with Marini winning twice. In 2020 Marini partnered Marco Bezzecchi: the combination of three wins and six podiums from Marini alongside two wins and seven podiums from Bezzecchi delivered VR46 their first Moto2 Teams' Championship. Marini and Bezzecchi finished second and fourth respectively in the riders' standings. The team's Moto2 entry was later absorbed into the Fantic brand structure from 2023.
In 2021 Luca Marini made his MotoGP premier class debut through an arrangement with Esponsorama Racing, competing under the Sky VR46 name and livery while Esponsorama handled racing operations. From 2022, VR46 Racing entered MotoGP in their own right, taking over the grid slots from Esponsorama Racing who departed the series. Marini and Bezzecchi formed the initial premier class line-up, riding Ducati Desmosedici machinery.
For 2023 the team retained both riders, using the older Ducati Desmosedici GP22. Bezzecchi emerged as one of the strongest performers in the first half of the season, winning in Argentina, France, and India, and briefly challenging for the Riders' Championship before injuries and the older specification hardware cost him ground in the latter stages. Indonesian lubricant brand Pertamina was announced as title sponsor from 2024, rebranding the team as Pertamina Enduro VR46 Racing Team.
Luca Marini left for Repsol Honda ahead of the 2024 season, replaced by Fabio Di Giannantonio. Marco Bezzecchi subsequently departed for Aprilia ahead of 2025, with Franco Morbidelli joining from Pramac Racing. From 2025, the team received full factory backing from Ducati, elevating VR46 from satellite to works status.
VR46 signed a partnership with Ducati in June 2021, initially as a satellite team using customer machinery. The relationship deepened progressively, with the team receiving the latest-specification Ducati Desmosedici. From 2025 the partnership was upgraded to full factory status, with Di Giannantonio assigned an official factory-backed Ducati Desmosedici through 2026. The team manager throughout the premier class era has been Pablo Nieto.
Across all categories, the VR46 Racing Team has accumulated 32 race victories: nine in Moto3, nineteen in Moto2, and four in MotoGP. Riders' Championship titles have been won by Francesco Bagnaia in Moto2 (2018) and Albert Arenas in Moto3 (2020, for Aspar, not VR46) — the team's own Moto2 Riders' Championship came with Bagnaia. The team also holds one Moto2 Teams' Championship, secured in 2020.