Mosca earned a degree in law from the University of Palermo in 1881. In 1887 he moved to Rome and took a position as editor of proceedings of the Chamber of Deputies of Italy. Having taught occasionally at Palermo and Rome, Mosca became chair of constitutional law at the University of Turin in 1896. He would hold this position until 1924, when he settled permanently in Rome to occupy the chair of public law at the University of Rome. Mosca held several other academic positions throughout his life.

In 1909 Mosca was elected to the Chamber of Deputies of Italy, in which he served until 1919. During this time, he served as Under-secretary for the Colonies from 1914 until 1916. In 1919, Mosca was nominated life senator of the Kingdom of Italy. He served actively in this capacity until 1926. During the Fascist dictatorship, Mosca retired to teach and research.

During this time, Mosca also worked as a political journalist for the Corriere della Sera of Milan (after 1901) and the Tribuna of Rome (from 1911 to 1921).

Mosca is most famous, however, for his works on political theory. These were Sulla teorica dei governi e sul governo parlamentare (Theory of Governments and Parliamentary Government), published in 1884; Elementi di scienza politica (The Ruling Class), published in 1896; and Storia delle dottrine politiche (History of Political Doctrines), published in 1936.

Mosca's enduring contribution to political science is the observation that all but the most primitive societies are ruled in fact, if not in theory, by a numerical minority. He named this minority the political class. Although his theory is correctly characterized as elitist, it should be observed that its basis is far different from The Power Elite described by, for example, C. Wright Mills. Unlike Mills and later sociologists, Mosca aimed to develop a universal theory of political society and his more general theory of the Political Class reflects this aim.

Mosca defined modern elites in term of their superior organisational skills. These organisational skills were especially useful in gaining political power in modern bureaucratic society. Nevertheless, Mosca's theory was more liberal than the elitist theory of, for example,Pareto, since in Mosca's conception, elites are not hereditary in nature and peoples from all classes of society can theoretically become "elite". He also adhered to the concept of "the circulation of elites," which is a dialectical theory of constant competition between elites, with one elite group replacing another repeatedly over time.