As a teenager, Daniel was taken in by Dan Call, a local lay preacher and moonshine distiller. He began learning the distilling trade from Call and his Master Distiller, Nathan "Nearest" Green, an enslaved African-American man. Green continued to work with Call after emancipation.
In 1875, on receiving an inheritance from his father's estate (following a long dispute with his siblings), Daniel founded a legally registered distilling business with Call, making Call the distillery's first Master Distiller. Daniel took over the distillery shortly afterwards when Call quit for religious reasons.
Daniel purchased the hollow and land where the distillery is now located. By the 1880s, Jack Daniel's was one of 15 distilleries operating in Moore County, and the second-most productive behind Tom Eaton's Distillery.
In 1907, due to failing health, Jack Daniel gave the distillery to two of his nephews. Motlow soon bought out the other nephew. He operated the distillery for about 40 years.
Daniel died in 1911 from blood poisoning.
The Jack Daniel Distillery in Lynchburg is situated in and around a hollow known as "Stillhouse Hollow" or "Jack Daniel's Hollow", where a spring flows from a cave at the base of a limestone cliff. The limestone removes iron from the water, making it ideal for distilling whiskey. Some 1.9 million barrels containing the ageing whiskey are stored in several dozen barrelhouses, some of which adorn the adjacent hilltops and are visible throughout Lynchburg.