McClure was born in 1906 in Blairsville, Pennsylvania.  Following his graduation from Westminster College in New Wilmington in 1928, McClure received a short-term appointment from the UPCNA Board of Foreign Missions to serve as a teacher in the Sudan.  After three years, he returned to the United States to attend Pittsburgh-Xenia Theological Seminary, graduating in 1934.

With his seminary degree in hand, McClure and his wife Lyda applied for regular foreign mission appointments and returned to the Sudan.  In 1952, McClure headed the new, ten-year Anuak Project, which deployed an increased number of missionaries to work with the Anuak tribe. In 1965, he took over as general secretary for mission work in Addis Ababa, Ethiopia, where he worked until retiring in 1971.

At the request of Haile Selassie, McClure then began work in an isolated area of eastern Ethiopia as part of the Godi Community Project.  On March 27, 1977, McClure and his son, fellow missionary Don McClure, Jr., went to Godi to close the mission station and transfer the work there to World Vision.  Somali guerillas attacked the station while they were there, killing the senior McClure, and wounding several others.