In 1944, aged 26, Mezzano was elected to the Michigan House of Representatives, as a representative of the Democratic Party. In July 1950, he was accompanying G. Mennen Williams, the Governor of Michigan, on a tour of the Marquette Branch Prison when the governor was attacked and briefly held hostage by inmates. All together, Mezzano won eight elections (including two unopposed, in 1954 and 1958) before losing to Joseph Mack in the Democratic primary in 1960. He was a Michigan delegate at the 1952, 1956, and 1960 Democratic National Conventions.