Born in Buddusò, Sardinia, into a working class family with Tuscan father and Venetian mother who found themselves in Sardinia on August 18, 1898. Biondetti's family moved from Sardinia back to Italy in the 1920s. He began racing at a relatively late age racing motorcycles in 1923 but in 1927 turned to automobiles and would swiftly become the Italian National Champion. By 1931 his performance earned him a spot in Grand Prix motor racing with the Maserati factory team. In 1934, he raced a private Maserati T26M. He sat out 1935 as his international license hadn't been renewed, probably due to political reasons. He continued as privateer in 1936, raced Alfas for Ferrari in 1937 and then as works driver for Alfa Corse during the 1938-40 era. 1938 saw the first victory in the Mille Miglia by Biondetti driving a new Alfa Romeo 8C by 3000cc dual compressor. Biondetti set a new record of the race at over 135 km on average, which was to remain unbeaten for fifteen years. After this success Biondetti should have been famous but he was an outspoken anti-fascist and the government conspired with the compromised national press to suppress any celebration of his victory. Unfortunately for Biondetti, he did not have Bracco's outgoing personality and the public did not rise to his defense.
During the war he secretly joined the partisans and by the time he was able to resume racing after the war, he was already 49 years old. Some Italians with long memories still resented him for his pre-war views. Nevertheless, he dominated Italian endurance racing, driving to victory in the Mille Miglia for three straight years from 1947 through 1949. In 1947 beating the Ferrari of the great Tazio Nuvolari in the pouring rain without the use of two gears. He also gained victories at the Targa Florio in 1948 and 1949. The approval of the Italian racing fans had finally come his way.
The 1947 Clemente Biondetti participated in one Formula one World Championship event, the 1950 Italian Grand Prix. Driving a self-built Ferrari-Jaguar hybrid car, engine problems forced him out of the race thus he failed to score any championship points. Biondetti had for a long time been suffering from cancer and he decided to retire from racing in 1954. He died in Florence early the following year at 57 years old.