Fausto Gresini founded the team in 1997 with Fabrizio Cecchini as technical director. The team competed in the 500 cc class with Brazilian rider Alex Barros on a Honda NSR500V two-cylinder bike. Barros finished ninth in the final championship standings and recorded the team's first podium finish at Donington Park. The following year Honda supplied Barros with the Honda NSR500 four-cylinder bike used by the factory team; Barros collected 138 points and fifth place in the final standings.
In 1999 the team dropped to the 250 cc class with a factory-supported Honda NSR250 and reigning 250cc world champion Loris Capirossi. At the first race of the season at Sepang, Malaysia, Capirossi took the team's first ever win. He added two more wins and six further podium finishes during the season, finishing third with 209 points.
After Capirossi moved to the 500 cc class for 2000, the team signed young Japanese rider Daijiro Kato and French rider Vincent Philippe. Kato had already won two races as a wild-card racer in 1997 and 1998 and made an immediate impression with four consecutive podium finishes at the start of the season. He became a title contender alongside Yamaha riders Shinya Nakano and Olivier Jacque until the final race at Phillip Island, Australia, where Kato finished third and lost the title and runner-up positions to Jacque and Nakano respectively. Kato's 259 points and third place earned him the Rookie of the Year award in the 250cc class.
In 2001 the team was renamed Telefónica Movistar Honda and former 125cc world champion Emilio Alzamora replaced Philippe. Kato dominated the season by winning 11 races, handing Gresini their first world title. Alzamora added two podium finishes, finishing seventh.
The team returned to the premier class in 2002 as Fortuna Honda Gresini. Due to rule changes the 500cc class became MotoGP and new 990cc four-stroke bikes were introduced. Kato rode the older Honda NSR500 two-stroke for the first nine races before receiving the new Honda RC211V ahead of the Czech Republic Grand Prix at Brno. He took a second place at the Spanish Grand Prix and matched that result at Brno. He also recorded the team's first MotoGP-class pole position at the Pacific Grand Prix at Motegi, Japan. Kato finished seventh in the final standings with 117 points and won the Rookie of the Year award. The team also ran Alzamora and Italian rider Roberto Rolfo in the 250cc class; Rolfo finished third with seven podium finishes.
In 2003 the team expanded its MotoGP effort to two riders and was renamed Telefónica Movistar Honda as Telefónica joined from Suzuki. Former Suzuki rider Sete Gibernau joined as the second rider while Kato was given the latest 2003-spec RC211V. In the opening race at Suzuka, Kato crashed into the tyre barrier, suffered serious injuries, fell into a coma for two weeks, and died in hospital. A week after Kato's death, Gibernau started from pole position and won the South African Grand Prix at Welkom — the team's first MotoGP-class race win. Gibernau dedicated the win to his late teammate. Japanese Supersport champion Ryuichi Kiyonari joined from the fourth race onwards. Gibernau won three more races and recorded ten total podium finishes, finishing second in the championship with 277 points. The team ranked fourth in the teams standings.
In 2004, Gibernau fought for the championship and finished runner-up. His teammate, Colin Edwards, finished fifth. Gibernau remained for 2005 alongside Marco Melandri, who won two races. In 2006 the lineup became Melandri and Toni Elías, with Elías bringing Fortuna sponsorship back to the team. The team achieved four victories: three for Melandri and one for Elías. Both riders remained in 2007, though Fortuna sponsorship ended due to European Tobacco Regulations. The team also switched tyre supplier to Bridgestone. The new 800cc Honda RC212V did not deliver expected results and the season yielded only two podiums.
For 2008, Alex de Angelis and Shinya Nakano joined under San Carlo sponsorship. In 2009 Elías returned, replacing Nakano who moved to World Superbikes. In 2010, Melandri re-joined alongside 2008 250cc champion Marco Simoncelli; Simoncelli finished eighth overall while Melandri finished tenth. For 2011, Simoncelli was promoted to a factory Honda within the Gresini team while Hiroshi Aoyama rode a satellite Honda. Simoncelli was competitive at the top of the field but crashes kept his points score low. On 23 October 2011, Simoncelli died after a racing accident at the Malaysian Grand Prix.
In 2015, Gresini ended their long-standing Honda partnership in the premier class. Aprilia returned to MotoGP with Gresini managing track-side operations. Aleix Espargaró scored Aprilia's first MotoGP-era podium and Gresini's first podium since the 2014 French Grand Prix with Álvaro Bautista at the 2021 British Grand Prix.
For 2022, Aprilia re-entered with their own factory team, taking Maverick Viñales and Espargaró. Gresini returned to fully independent status with Ducati machinery, fielding former Gresini Moto3 teammates Enea Bastianini and Fabio Di Giannantonio. Bastianini secured the team's first-ever premier class victory at the season-opening Qatar Grand Prix and added wins in the United States, France, and Aragon. Di Giannantonio secured the team's first-ever pole position at Mugello. Bastianini finished third in the riders' championship and was promoted to the Ducati factory team for 2023, replaced by Álex Márquez from LCR Honda. Di Giannantonio took a feature race win at the 2023 Qatar Grand Prix, with Álex Márquez taking the team's first sprint victories at Silverstone and Sepang.
Eight-time world champion Marc Márquez joined Gresini for 2024, after 11 years with Repsol Honda, pairing with his brother Álex. The Márquez brothers most notably shared a podium at the 2024 German Grand Prix, 27 years after the Aoki brothers, Nobuatsu and Takuma, did the same at the 1997 City of Imola Grand Prix. All three of Gresini's 2024 victories came from Marc Márquez — at Aragon, Misano, and Phillip Island — and he finished third in the championship.
For 2025 and 2026, Spanish rookie Fermín Aldeguer replaced Marc Márquez, who moved to Ducati Corse. Álex Márquez secured his maiden Grand Prix victory at Jerez. Aldeguer claimed his maiden MotoGP victory at the Indonesian Grand Prix, becoming the first independent team rider since Jorge Martín in 2021 to win in a rookie season. At the Malaysian Grand Prix, the team clinched the independent team of the year title; Álex Márquez finished runner-up in the championship with his third victory of the season, and Aldeguer won the Rookie of the Year award. The team described 2025 as their best season since Melandri's runner-up finish in 2005.
The team has competed in Moto2 since 2010. Gresini rider Toni Elías won the inaugural Moto2 title on a Honda-powered Moriwaki chassis. The team was formerly known as QJmotor Gresini Racing before Gresini ended that sponsorship in 2024.
The team competed in Moto3 from 2012 to 2021. From 2015 the team used Honda machinery, replacing KTM. In 2018 Gresini achieved a 1-2 championship finish in Moto3 with riders Jorge Martín and Fabio Di Giannantonio. Gresini exited Moto3 in 2021 to focus on MotoGP and Moto2.
In 2019 Gresini was granted two slots in the newly created MotoE class. Rider Matteo Ferrari clinched the inaugural MotoE Cup with two wins and multiple top-five finishes.
Fausto Gresini (1961–2021), a two-time 125cc world champion, founded the team in 1997 following the end of his racing career. On 23 February 2021, Fausto Gresini died after a two-month battle with COVID-19. His wife Nadia Padovani took over as team owner and principal.
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