Knob Lick is an unincorporated community in southern Saint Francois County, Missouri, United States. It is located on U.S. Route 67 about eight miles south of Farmington. Knob Lick has a post office with zip code 63651.
The community was named in 1876 for the nearby Knob Lick Mountain. In the Ozarks, knob typically refers to an isolated summit, and lick is a natural "salt lick" or salt spring. The salt lick was once frequented by buffalo. The mountain is across U.S. Route 67 from the town at . Eighty of the summit are protected by the Missouri Department of Conservation. A gravel road leads to the conservation area which includes a granite glade, picnic facilities, and a closed fire lookout tower.
The St. Louis and Iron Mountain Railroad had a stop at Knob Lick that was a shipping point for granite mines in the area. There were also lead mines nearby, including Mine La Motte. Knob Lick has been home to the S-F Scout Ranch since 1965.