Preaching ran in Mordecai Ham's family. Both his grandfather, for whom he was named, and his father pastored numerous churches in the small Kentucky communities where he was raised.

Mordecai Ham first felt the call to preach at age nine, but he resisted until his grandfather's death in 1899. At that time, Ham entered the field of evangelism, traveling and preaching across Kentucky. The results from those early meetings were so great that he was in great demand throughout the South.

Ham and his song leader, W. J. Ramsey (known as the Ham and the Ram) saw over 300,000 converts baptized into Baptist churches between 1902 and 1940. Over 7,000 people surrendered to full-time Christian service under his preaching. Ham stayed in evangelism full-time except for a brief stint as pastor of the First Baptist Church in Oklahoma City 1927-1929.

Along with Billy Sunday, he led in the fight for Prohibition, and then later against its repeal.

After 1941 Mordecai Ham focused on a growing radio ministry and shorter meetings in churches. God continued to use him for another twenty years to bring hundreds more to faith in Christ.