The son of Abel James, a Philadelphia merchant, Thomas Chalkley James acquired a love for literature at the Quaker academy where he was educated by Robert Proud. He studied medicine at the University of Pennsylvania (B.A. 1787) and served as a surgeon in the merchant marine. After medical studies in London and Edinburgh he taught obstetrics at the Pennsylvania and edited the Eclectic Repertory and Analytical Review. A bibliophile and antiquary, James was one of the circle involved with publishing the Port Folio in Pennsylvania, writing under the initials "P. D." He was a founder and president of the Union Benevolent Association, and one of the founders of the Historical Society of Pennsylvania.