Handling serpents as a form of Christian worship originated in Tennessee and dates back to the early 1900s. Historians recognize George Hensley, an illiterate Church of God evangelist, as the founder. Hensley lived with his family in Grasshopper Valley, Tennessee, near Chattanooga. His son, James, credited Amanda, George Hensley's wife, as being the spiritual leader of the family.

George, while pondering the passage in Mark 16:17—18 which says that believers shall take up serpents, climbed White Oak Mountain and prayed for a sign. It was there that he spotted a large rattlesnake, put the snake in a gunnysack and took it to a revival meeting. George stood up and cited the gospel text, handled the serpent himself, and then challenged the people to prove their faith by doing the same.

As serpent handlers headed north during the 1920s and 1930s, they found a ready reception among some miners in Kentucky and West Virginia. Few of the early serpent handlers in West Virginia ever met George Hensley. Their prophet was Kentuckian Raymond Hayes. Hayes made a trip to Fayette County in 1946 and visited with Elsie Preast, who began to handle serpents regularly at the Church of All Nations. Preast said he knew that serpent handling had been practiced 17 to 18 years earlier on Cabin Creek, near Charleston.

West Virginia is the only state that legally permits serpent handling. At the turn of the 21st century, the most active serpent handling church in West Virginia was located near Jolo, McDowell County, where Robert and Barbara Elkins, along with Dewey Chapin, her son, were the leaders. Other important leaders over the years in the serpent handling churches in West Virginia were Joe and Myrtle Turner and their family at Camp Creek, Boone County, and Brother Hammonds and his wife at Fraziers Bottom, Putnam County.

In a serpent handling church, one may observe not only preaching, praying aloud together on one's knees, dancing and singing but also serpent handling, fire dancing, speaking in tongues, the laying on of hands for healing, testimonies, and at times, poison drinking and foot washing. An observer may also witness "stigmata," the oozing of blood from the hands or feet in empathy with the death of Jesus.

Serpent handling functions sacramentally in the lives of these Christians. When they pick up a snake, constantly calling upon the name of Jesus, they celebrate the central truth of the Gospel, that "through faith in Jesus there is victory over death"; and they experience, in a most dramatic way, that not even a serpent bite can separate them from eternal life with Jesus.