Born in Scranton, Pennsylvania, Luce was first a supporter and later a recruit of the Student Volunteer Movement (SVM), and a lifelong friend of Sherwood Eddy, John R. Mott, and Robert E. Speer. His commitment to missions came during his time at Yale University, from which he was graduated in 1892. He spent two years at Union Seminary (New York), and completed his seminary training at Princeton in 1896. He devoted two years---the year before graduating from Princeton, and the year following graduation---to the promotion of SVM.
In 1897 he was ordained, married, and appointed by the Presbyterian Board of Foreign Missions for service in China, where he spent 31 years. Luce was a professor in Shantung Christian (Cheeloo) University founded by Calvin Mateer and later vice-president of Yenching University in Peking. Distinguished in appearance, convivial, and persuasive, he raised sizable amounts of money for both Chinese institutions, enabling them to become renowned Christian schools of higher learning. He published five books in Chinese and helped initiate the Yale-in-China Association. He resigned in 1928 to accept a professorship at the Kennedy School of Missions in Hartford, Connecticut, from which he retired in 1935.
Luce devoted the remaining six years of his life principally to two endeavors: the Associated Boards for Christian Colleges in China, and conference-like "institutes" he initiated to help North Americans become aware of what he called the "other five-sixths of the world." He is buried in Utica, New York. One of his four children, Henry R. Luce, was the founder and longtime editor-in-chief at Time-Life.