For the first time Masetti competed in the first year of the motorcycle world championship in 1949 (125 cm³ class) with a Morini . In the 1950 season , he won the world championship in the class up to 500 cm³ with a Gilera with a narrow margin over Geoff Duke ( Norton ) . The following year he won the Grand Prix of Spain and in 1952 again the half-liter World Cup. In the 1953 season Masetti started for NSU in the class up to 250 cm³, but had an accident in Imola , so that he could no longer participate in the season. The following year he again competed with Gilera in the 500cc class and came in second behind his old rival Geoff Duke. From 1955 Masetti drove for MV Agusta and retired from motorsport in 1958 after a less than successful season.
Umberto Masetti then lived in Maranello and died there on May 28, 2006 at the age of 80 from a respiratory disease.