Receiving his early education in Ireland, James returned to the United States and was ordained 30 June 1861 in the Archdiocese of Baltimore, Maryland. Vicar Apostolic of North Carolina and Titular Bishop of Adramyttium on 3 March 1868. Bishop of Richmond, Virginia on 30 July 1872. Coadjutor Archbishop of Baltimore and Titular Archbishop of Ionopolis on 20 May 1877. He succeeded to the archbishopric on 3 October 1877. Cardinal–Priest of San Maria in Trastevere on 7 June 1886. Participated in the 1903 conclave that elected Pope Saint Pius X. Council Father at the First Vatican Council.
He occupied a conspicuous place in American public life as priest, prelate, patriot, controversialist, writer, and interpreter of the doctrines of the Catholic Church. Appointed Apostolic Delegate to the Third Plenary Council of Baltimore, he proved that there was no antagonism between the Catholic Church and progress, science, and sound industrial and political theories. He championed the rights of labor, and one of his ablest documents was a famous plea contained in his letter on the Knights of Labor to the Prefect of the Congregation for the Evangelization of Peoples, 28 February 1887. Pope Leo XIII‘s encyclical on labor, which soon followed, proved he had won every point for which he contended. Due to his interposition, the question of the sale of the Friar Lands in the Philippines was arranged. He took an invaluable part in adjusting the ecclesiastical status in Cuba and Puerto Rico after the Spanish-American War. During World War I he organized the National Catholic War Council and the National Catholic Welfare Council. His book , a clear, simple exposition of the Catholic Faith, was one of the most remarkable books written in the 19th century. He also wrote and . He was remarkable for piety and sagacity.