In September 2014, KTM motorsport director Pit Beirer announced the manufacturer's intention to enter MotoGP from the 2017 season. Development of the RC16 — a V4-engined machine using a steel trellis frame, a chassis concept unique to KTM in the MotoGP paddock — began in earnest thereafter. In October 2015, the RC16 completed its first track test at the Red Bull Ring with Alex Hofmann as test rider. Subsequent development testing involved Mika Kallio, Randy de Puniet, Karel Abraham, and Thomas Lüthi at circuits including Jerez, Brno, Misano, and Mugello.
The bike was presented publicly before the 2016 Austrian Grand Prix, with test riders Kallio and Hofmann demonstrating it to spectators. Kallio made the RC16's official racing debut as a wildcard entry at the 2016 Valencian Grand Prix, qualifying twentieth and running with the pack before a rear wheel sensor malfunction forced retirement. It was nonetheless the machine's competition baptism.
Winter testing for the full 2017 programme was led by Pol Espargaró and Bradley Smith, who joined as the team's first full-time MotoGP riders after three seasons as teammates at the Yamaha Tech 3 satellite squad.
KTM made their full MotoGP grid debut at the 2017 Qatar Grand Prix, qualifying twenty-second and twenty-third and finishing sixteenth and seventeenth. The team scored their first championship points in the second round in Argentina. Espargaró achieved the team's first top-ten finish at the Czech Republic Grand Prix, placing ninth.
The 2018 season brought mixed progress. Espargaró scored points consistently in the early rounds, while Johann Zarco was announced as Smith's replacement for 2019. Injuries hampered both Espargaró and Kallio — who suffered a serious knee injury during practice at the German Grand Prix — but the season concluded with a landmark result. At the 2018 Valencian Grand Prix, Espargaró achieved KTM's first MotoGP podium with third place, in wet conditions that showcased the RC16's adaptability. Smith ended his KTM tenure with a personal-best eighth.
Johann Zarco signed for 2019 but announced mid-season that he would not continue beyond that year. He did not complete the full campaign, with Mika Kallio returning as replacement for the final rounds.
On 9 August 2020, Brad Binder won the Czech Grand Prix at Brno, delivering KTM's first-ever MotoGP victory and first dry-weather podium in a single result. The win arrived less than four full seasons after the team's debut and underlined the rapid development curve the RC16 had undergone.
KTM has developed a structured talent pathway — the KTM GP Academy — designed to identify and support young riders from development series including the Red Bull MotoGP Rookies Cup, the Northern Talent Cup, and the Austrian Junior Cup, progressively through Moto3 and Moto2 before elevation to MotoGP. Graduates of this system include Brad Binder, Miguel Oliveira, Remy Gardner, Augusto Fernandez, and Pedro Acosta, the latter winning two titles in three seasons of Grand Prix competition before reaching MotoGP.
KTM's MotoGP programme represents a rare successful entry from a non-Japanese, non-Italian manufacturer into the premier class of motorcycle racing. The RC16's unconventional steel trellis frame and V4 layout reflect the manufacturer's willingness to pursue its own engineering identity rather than conforming to the aluminium-twin-spar convention used by the Japanese factories. The KTM GP Academy model of vertical talent integration has been praised across the paddock as a template for sustainable manufacturer involvement in the sport.