In "a New England city", Frank Skeffington (Spencer Tracy) plans to run for a fifth term. Skeffington rose from poverty in an Irish ghetto to become mayor and former governor, and is skilled at using the power of his office and an enormous political machine of ward heelers to receive support from his Irish Catholic base and other demographics. Rumors of graft and abuse of power are widespread, however, and the Protestant bishop, newspaper publisher Amos Force (John Carradine), banker Norman Cass (Basil Rathbone), and other members of the city's traditional elite the Irish Catholics replaced oppose Skeffington; so do the Catholic cardinal (Donald Crisp), Skeffington's childhood friend, and other Catholics. Skeffington's opponents support the candidacy of Kevin McCluskey (Charles B. Fitzsimons), a young Catholic lawyer and war veteran with no political experience.