As a teenager, Daniel was taken in by a local pious Lutheran Minister and moonshine distiller named Reverend Daniel Call and he began learning the distilling trade from him. Within three years around 1866, Jack became a full partner in the small distillery at the Call farm off Louse Creek. In 1875, upon receiving an inheritance from his father's estate following a long dispute with what was left of his siblings, Jack founded and legally registered a whiskey distillery with Call. He took over the distillery shortly afterward when Call was forced to quit by his wife and Congregation for religious reasons. He was given the choice between Whiskey and Religion and chose god. At that facility, Jack learned the everyday operational tasks and the tricks of the trade from an enslaved African American named Nathan "Nearest Green" (1840-1890). Nearest essentially served as "Master Distiller" for the distillery and remained working for Jack even after emancipation at the conclusion of the Civil War.

On the bottle itself the label says "Est. & Reg., in 1866,"  but Daniel's biographer has cited official documents that say the business was not registered until Jack's inheritance in 1875 but that Jack knew the older the distillery was, the more people would trust his product's quality.

After taking over the distillery completely in 1884, Jack purchased the hollow and land where the distillery is now located about five miles from where Jack was born. There is an underwater spring runs throughout the property and even under the distillery. The cave goes back into a hillside about a mile and cuts through layers of limestone, keeping the water at a cool 56 degrees year-round. The limestone-filtered water is the most important feature of all Jack Daniel’s whiskies. It not only removes unfriendly iron from the water, but also adds calcium and magnesium. That spring has been listed as South Central Tennessee's most important natural resource by Forbes Magazine in 2008. He began using a square shaped bottle in 1897, the shape that Jack said intended to convey a sense of fairness and integrity.  More importantly, it distinguished his bottles from everyone else's bottle on the market.

The distillery will tell you that the origin of the "Old No. 7" brand name was because it was the 7th Recipe that Jack had tried, and apparently, the one that he liked best.  But in reality, the number was assigned to Jack's distillery for their government registration in which he was the No. 7 distillery in district 4 of the U. S.  At one point He was forced to change the registration number when the federal government redrew the district lines and he became No. 16 in district 5, instead of his original number seven. However, he continued to use his first distillery designation as the brand name in "Old No. 7," since his brand and reputation already had been established using that description.

Jack Daniel's experienced a huge surge in popularity around the country after the whiskey received the Gold Medal for the finest whiskey at the 1904 World's Fair in St. Louis, Missouri. At that same time, Jack Daniel's local reputation in Tennessee was suffering because the temperance movement was sweeping the state. That gold medal would be the first of seven that the brand would go on to earn.

ack Daniel never married and did not have any children. In order to continue his success, Jack brought in his two nephews from his sister Finetta Josephine "Josie" Daniel Motlow and her husband Felix "Stump" Motlow to help run the place. Josie was only a year older than Jack and was by far his closest sibling.  His nephews Lemuel Oscar "Lem" Motlow (1869–1947) would run the business side of the distillery while Jesse Butler "Jess" Motlow (1897-1957) ran the production or distilling side of things, both under Jack's guidance. Lem was skilled with numbers and was soon doing all of the distillery's bookkeeping and accounting.

In 1907, due to failing health, Jack Daniel gave the distillery to two of his nephews.  Lem soon bought out Jess's shares and went on to operate the distillery for about 40 years. He named Jess Motlow the company's second Master Distiller in 1907. This was a job he did well and would hold until 1941.

Tennessee passed a statewide prohibition law in 1910. This effectively barred the legal distillation of whiskey within the state. Motlow challenged the law in the Tennessee Supreme Court but the court upheld the law as constitutional.

Jack died in 1911 from blood poisoning. The distillery claims that an infection began in one of his toes, which Daniel injured one early morning at the distillery’s office when he kicked the safe in anger when he could not get it open. It is said that Jack always had trouble remembering the combination to that safe.