MotoGP is the successor to the 500cc class. The main motorcycle manufacturers, actually the four big Japanese brands (Honda, Yamaha, Suzuki and Kawasaki), had not considered this class to be a good reflection of the commercial market for street motorcycles for some time. In consultation with the organising FIM, it was decided to create a four-stroke class in which the machines were limited to 990 cc. European factories such as Ducati also decided to enter this new class, along with a few smaller manufacturers. In 2001, the first MotoGP machines were raced together with the 500cc two-stroke machines in the last 500cc season.

The following year was the first full MotoGP season. In addition, the number of races per season was expanded to 18 in the 2007 season. The only circuit that has been involved since the start of GP racing in 1949 is the Circuit van Drenthe, where the TT was held every last Saturday in June. From 2016 onwards, the race will be held on Sundays.

Valentino Rossi, riding with his permanent number 46, became the first world champion in this class and repeated this in the following three seasons. Before the start of the 2004 season, he made a much-discussed switch from Honda to Yamaha. Nicky Hayden won the title in 2006 and Casey Stoner in 2007. Other well-known riders include Sete Gibernau, Marco Melandri, Dani Pedrosa, Marc Marquez and Jorge Lorenzo.