Justino de Azcárate Flores was born in León, Spain, on 26 June 1903. He was from a prominent liberal intellectual family of León. His family was Basque in origin, but an ancestor who was an official in the King's Treasury had settled in León in 1690. His grandfather, Patricio de Azcárate, was governor of several provinces, translated the complete works of Plato and Aristotle, and also translated works of Gottfried Wilhelm Leibniz. His uncle was Gumersindo de Azcárate, a scholar, lawyer and Republican deputy of León for thirty years, head of the Republican-Socialist minority until shortly before his death in 1917. His father made his career in the army. Justino's older brother Pablo de Azcárate (1890–1971) became a deputy of León and then ambassador to the United Kingdom during the Second Spanish Republic.
Justino de Azcárate was brought up in a prosperous household and was educated in English, and then at the German school for five years. After this he went to the Residencia de Estudiantes in Madrid where he finished the baccalaureate, and then began to study Law. After graduating he was assistant to Adolfo González Posada(es) at the university. He was deeply involved in the movement to overthrow the dictatorship of Miguel Primo de Rivera. He knew socialists such as Julián Besteiro and Fernando de los Ríos, but was not a socialist himself. He became secretary to the group of intellectuals Al Servicio de la República(es). Fernando de los Ríos came to hide in his house after the repression that followed the Jaca uprising of 12 December 1930. It was in his house that Francisco Largo Caballero and the others decided to surrender to the government and go to jail.