William Cocke was educated at home and read law, gaining admission to the bar in Virginia. He spent several years in public service, including roles in the Virginia House of Burgesses and the Congress of the Confederation for the State of Franklin. Cocke transitioned to Tennessee, where he participated in drafting the state's first constitution and served in the U.S. Senate. He also held judicial positions, including a judgeship in the First Circuit Court of Tennessee, though he faced impeachment and removal from office. Cocke's career included significant involvement in military and Indian affairs, culminating in his appointment as an Indian agent to the Chickasaw nation.

William Cocke's political career reveals a man who navigated complex regional interests with a blend of localism and strategic alliances. His military record, marked by accusations of cowardice, contrasts sharply with his later role as an Indian agent, suggesting a multifaceted approach to frontier governance. Cocke's judicial career ended abruptly with impeachment and conviction, hinting at a contentious relationship with state authorities. Despite these controversies, his legacy endures through familial political influence and the naming of Cocke County, Tennessee.