Born in Cannes, Zarco moved into minimoto championships in 2004 and competed primarily in Italy. He was runner-up in the Senior Mini European Championship in 2005 and runner-up in the European Open Championship in 2006. In 2007 he entered the Red Bull MotoGP Rookies Cup and won the championship at Estoril, taking four race victories across the season. His performances brought him into the Red Bull MotoGP Academy alongside Cameron Beaubier, Jonas Folger, and Danny Kent.
Zarco made his Grand Prix debut in 2009 with the WTR San Marino team at Qatar, finishing fifteenth in a rain-shortened race. He spent two seasons in 125cc, steadily improving and finishing eleventh in the 2010 championship. In 2011 he joined Ajo Motorsport and earned his first 125cc podium — a third place — at the Spanish Grand Prix.
Zarco moved to Moto2 with the JiR team in 2012, riding Motobi machinery. He finished tenth in the standings in his debut year, easily the highest-placed rookie. After moving to Ioda Project Racing Team in 2013, he collected two podiums and improved to ninth. For 2014 he joined the new Caterham Moto Racing team and impressed on what was considered an inferior Kalex-rival package, earning four podiums, one pole position, and sixth in the championship.
Zarco joined Ajo Motorsport for 2015 and dominated the intermediate class. He won eight races, stood on the podium fourteen times, claimed seven pole positions, and finished with a championship-record 352 points and a winning margin of 118 points — both Moto2 era records. He repeated the championship in 2016 with seven wins, ten podiums, seven poles, and 276 points, becoming the first rider to retain the Moto2 title. His backflip celebration after victories became a signature spectacle for fans across the paddock.
Zarco graduated to MotoGP in 2017 with the Monster Yamaha Tech3 satellite team. On debut at Qatar he seized the lead on the opening lap before crashing out on lap six. He recovered to take his first MotoGP podium — second place — at his home French Grand Prix at Le Mans. He won the Rookie of the Year Award, finished sixth in the championship as the highest-placed independent rider, and backed it up with two pole positions at Assen and Japan.
In 2018 Zarco continued with Tech3, adding further pole positions and two second-place finishes in Argentina and Spain. He again finished sixth in the standings.
Zarco signed a two-year KTM factory contract starting 2019 but struggled badly with the RC16. At KTM's home Austrian Grand Prix the two parties announced a mutual agreement to end the contract, and Zarco was released after the Misano round, replaced by test rider Mika Kallio for the remaining races.
For the final three races of 2019 Zarco stepped in at LCR Honda, covering for the injured Takaaki Nakagami. He signed with Avintia Esponsorama Racing for 2020 on a Ducati, taking the team's first ever pole position at Brno and backing it with a podium finish the next day.
Zarco moved to the Pramac Ducati satellite team in 2021 and enjoyed the most productive period of his MotoGP career: he finished fifth in the 2021 championship — his career-best position — racking up a then-career-high points total. He remained with Pramac for 2022 (four podiums, eighth in standings) and 2023. After 120 MotoGP races without a top-class victory, he finally broke through in Australia in 2023, overtaking teammate Jorge Martin on the final lap.
Zarco moved to LCR Honda for 2024 rather than accept Ducati's offer of a single-year contract before a switch to Superbike racing. He was the top Honda finisher in both 2024 and 2025. At the 2025 French Grand Prix at Le Mans he became the first French rider to win on home soil in 71 years and the first non-Ducati rider to win a feature race in 22 rounds. The following race at Silverstone he finished second, marking the first back-to-back podium for any Honda rider since Marc Márquez in 2021. He extended his LCR contract through 2026 and 2027 in September 2025.
Zarco holds several Moto2 era records: most championships won (two, 2015 and 2016), highest points total in a single season (352 in 2015, shared in podium terms with Marc Márquez, Esteve Rabat, and Pedro Acosta), most consecutive podiums (twelve), and the largest title-winning margin by points (118 in 2015). His two consecutive Moto2 titles remain unique in the class's history, and his eventual MotoGP breakthrough win in Australia 2023 came after one of the most patient campaigns in modern Grand Prix racing.