He played a prominent role in the Council of Basle and was in touch with the leading humanists of his day, such as Nicholas of Cusa.
Nothing is known of him before he took part in the Council of Basle, except that he was archdeacon at Villaviciosa, canon at Toledo, and professor of theology at the University of Salamanca, but it has been hypothesized that he was one of the sons of Diego Gonzalez of Contreras and Angelina of Greece.
After Eugene IV was deposed by the council on 25 June 1439, John of Segovia was appointed on the committee whose duty it was to select a number of theologians to elect the new pope.
At the end of the schism in 1449 he resigned the cardinalate, was appointed titular Bishop of Caesarea by Eugene IV, and retired to a monastery.
John spent much of his retirement in Aiton advocating peaceful dialogue with the Islamic world and the translation of the Koran into Western languages, Castilian, with the assistance of an Islamic scholar, Içe de Gebir.