William Clark, youngest brother of George Rogers Clark and Lucy Clark Croghan, moved from Virginia to Kentucky with his parents in 1784. Beginning in 1789 he served in a number of military expeditions against the native Americans of the developing lands of the backcountry, including missions to contain the Creek and Cherokee nations and expeditions under Generals Scott and Wilkinson against the native Americans on the Wabash. He was commissioned as a first lieutenant in the 4th Sub Legion under General Wayne in March 1793.
Returning to Kentucky in 1796, Clark lived with his parents at their Mulberry Hill farm near Louisville. When they died, he inherited the homestead but sold it to his eldest brother, Jonathan, in 1800 and moved to Clarksville, Indiana, with his brother, George Rogers Clark.