Zana started to work as a tailor in Silvan after he graduated from elementary school. In 1963 he became a member of Workers Party of Turkey (TİP). Two years later he became the head of the party's Silvan branch.
In 1978 he was elected as the first independent socialist mayor of Diyarbakır. After 1980 Turkish coup d'état, which made the Workers Party illegal, he was imprisoned in the Military Prison of Diyarbakır and incarcerated for 16 years. Zana then lived in Sweden and Germany, at last returning to Turkey in 2004.
Mehdi Zana has been married to politician Leyla Zana since 1975 and the couple has two children.