Red-haired William Clark stood six feet tall, had a strong physique, and at age thirty-three was four years older than Lewis. He had been born in 1770 of Scottish descent on a farm in Caroline County, Virginia. His father, John, had inherited the farm from a bachelor uncle and brought his family there about 1755 from a log cabin at the present northeastern edge of Charlottesville - where they had known the Jeffersons. William was the youngest of six sons and the ninth child in a family of ten children. All his older brothers fought in the War for Independence. Four of the six sons, including William, went on to become officers.

In 1784, when William was only fourteen, John set out with his family for the Kentucky country. After an icebound winter on the Monongahela near Pittsburgh, in the spring they floated down the Ohio with other westbound emigrants to Louisville. It had grown up around a fort that William's older brother, George Rogers Clark, had founded in 1778-79 as a headquarters during his campaign against the British. John settled along Bear Grass Creek near the fort and soon built Mulberry Hill. There on the frontier William received limited formal schooling, but he was interested in Indians and worshipped George Rogers, who probably taught him something about soldiering, woodcraft, and the Indians. By the time he was nineteen, the youth had joined the militia where he soon gained a captaincy.