In 1776, as a colonel of militia, he led a company of men into North Carolina's Washington District for action against the Indians.

The newly formed government selected Cocke to be one of the new state's initial senators, along with William Blount.

The Federalist Senate held by a narrow margin (11–10) that Cocke and Blount's election was illegal because it had occurred without congressional authorization.

The Tennessee General Assembly, however, neglected to elect a successor to Cocke; he was subsequently appointed to his former seat by Governor John Sevier on April 22, 1797, until the General Assembly belatedly elected his successor, Andrew Jackson.

He was involved in exploration while in the company of Daniel Boone, traveling through much of what was to become eastern Kentucky and East Tennessee.

He briefly returned to military duty, serving under Andrew Jackson in the Creek War.