Gaetano Salvemini was born in Molfetta, in the Apulia region of southern Italy, to an impoverished family with left-wing politics that shaped his own political and social ideals. He won a scholarship to attend the University of Florence, where he eventually earned a PhD and met his first wife Maria Minervini. In 1899, he published his first book, Magnati e popolani nelle commune di Firenze 1280-1295, now considered a classic that introduced economic and social analysis into Italian historiography. He was appointed professor in medieval and modern history at the University of Messina in 1901. He worked to promote universal suffrage and universal education, and wrote La Rivoluzione francese (The French Revolution, 1905) and the first major analysis of the ideas of Mazzini (1905). The 1908 Messina earthquake killed his wife, their children and his sister before his eyes in their home. He went on to teach history at the University of Pisa and the University of Florence. He founded a new socialist journal, L'unita. In 1919, he was elected to Parliament but in 1921, after the Fascist regime came to power in Italy, he withdrew from politics.
In 1925, he was arrested for secret anti-Fascist activities, but managed to flee the country. In exile, he helped establish a new international anti-Fascist organization called Giustizia e Libertà. In 1933, he emigrated to the USA and was awarded a chair in Italian history and culture at Harvard, where he taught until in 1948. Prior to World War II, he worked to awaken the people of the USA and UK to the dangers of fascism. In 1948, Salvemini retired to Italy, where he continued to participate in Italian culture and politics and maintain contact with American friends and policymakers whose attitudes he helped to shape, such as H. Stuart Hughes, Ruth Draper, Water Lippmann, Felix Frankfurter, and Arthur Schlessinger, Sr. He contributed articles to publications such as Il Ponte, Critica Sociale, and Il Mondo into his 80s.