Born in Winnsboro, South Carolina, Mills graduated from Davidson College (BA, 1903), Davidson, South Carolina. He taught for three years in Camden, South Carolina, then did a year of graduate study at the University of South Carolina (M.A., 1907). One of the early Rhodes Scholars at Christ Church College, the University of Oxford, Mills graduated with honors in theology (B.A. 1910). He was YMCA secretary at the University of South Carolina from 1910 to 1912. During this time he also studied at Columbia (South Carolina) Theological Seminary (B.D., 1912). In 1932 he received an S.T.M. degree from Union Theological Seminary, New York, and in 1951 an honorary D.D. from Davidson College. He served under the YMCA in China from 1912 to 1932, largely in ministry to students.
In 1932 Mills resigned from the YMCA, was ordained, and began work under the Presbyterian Foreign Mission Board in Nanking (Nanjing), where he coordinated the work of the Presbyterian mission and worked with Chinese pastors. Just before the Japanese occupation of Nanking, Mills played an important role in efforts to bring about a truce that would allow the Chinese army to withdraw from Nanking and the Japanese army to enter the city without fighting. With approval from General Tang Sheng-chih, Mills and fellow missionary M. Searle Bates went to see the U. S. consul, J. Hall Paxton, on board the USS Panay, to transmit the truce-negotiating messages.
After the Japanese army occupied Nanking, Mills was appointed vice-chairman of the International Committee for the Nanking Safety Zone when it was founded in November 1937, and chairman in February 1938. The Nanking Safety Zone had a population of about 250,000, of which about 70,000 people were dependent upon the zone committee for food and fuel. Mills received the Order of the Green Jade, the highest honor given to Westerners by the Chinese government in recognition of his work in Nanking during 1937-1938. During World War II he was interned for nine months in Shanghai by the Japanese, was repatriated in 1943, and returned to China in 1944.
The next five years were spent in Chungking (Chonqing) and Shanghai. He left China in 1949 and retired formally in 1951 but continued to work in New York City on the staff of the Missionary Research Library at Union Theological Seminary until 1955. He died in New York City.