However, he had a divine call to the regions beyond, so he resigned his faculty position and entered the Presbyterian Seminary in Chicago. He graduated in the spring of 1892 and sailed for India the following October. His ministry of prayer in India during the next twenty years was so well known that the natives referred to him as "the man who never sleeps." Also, he was called the "Apostle of Prayer," but more familiarly he was known as "Praying Hyde."

John Hyde was all these and more, for deep in India he sought the Lord, and the strength of meeting his Master face to face prepared him for missionary service. Often he spent thirty days and nights in prayer and many times was on his knees in deep intercession for thirty-six hours at a time. His work among the villages was so successful that for years he led four to ten people a day to the Lord Jesus Christ.

Hyde was instrumental in establishing the annual Sialkot Conferences, from which thousands of missionaries and native workers returned to their stations with new power for the work of reaching India with the Gospel. Hyde's life of sacrifice, humility, love for souls and deep spirituality, as well as his example in the ministry of intercession, inspired many to follow his example in their own lives and ministries. He died February 17, 1912. His last words were: "Shout the victory of Jesus Christ."