Schlesser began his motor sport career in 1952, when he rallied a Panhard before, in 1954, trying the then popular French class of racing known as
Monomill. His career was then interrupted for three years whilst he was working in Mozambique but he returned to Europe in 1957 when he finished second in the Rome–Liège–Rome Rally in a Mercedes. He then raced a Ferrari 250 GT but without much success until 1960 when he finished second in class at the Nürburgring 1000 km and second overall at Rouen. He also raced a Cooper in Formula Two in 1960 but only achieved a sixth place at Syracuse. In 1961 his season was cut short by an accident at Le Mans but he returned in 1962 with a Formula Junior Brabham.
In 1964 Schlesser moved to the new one-litre Formula Two and became a highly regarded competitor in European Formula Two in the pre-European Formula Two Championship era. In 1966 he joined the works Matra Formula Two team and continued with the same team as Ford France in 1967. In 1968 he joined his close friend Guy Ligier to race McLarens.
Jo Schlesser also raced in NASCAR, finishing 13th in the 1964 Daytona 500.