The fort was subject to two major sieges, two notable feats (McColloch's Leap and Betty Zane's trek through the battle) and other skirmishes.

The outbreak of Lord Dunmore's War, a conflict between American Indians of the Ohio Country and Virginia, was the immediate reason for its construction.

Construction was supervised by Colonel William Crawford under the orders of the Royal Governor of Virginia, Lord Dunmore.

It would appear that the need for a fortified shelter was noticed simultaneously by the residents of the area, and by the military authorities at Fort Pitt (Pennsylvania), in the spring of 1774.

A letter preserved in the Pennsylvania Archives shows that Connolly told Crawford "to proceed to Zanesburg and complete the fort."

On the south and west (river) sides, the bluff prevented or greatly hindered assaults.

In 1777, Native Americans of the Shawnee, Wyandot and Mingo tribes joined to attack colonial settlements along the Ohio River.

The Indians rushed to the edge, expecting to see the Major lying dead in a crumpled heap at the bottom of the hill.

[citation needed] The fort was dismantled soon after the end of the Revolutionary War, though some parts of it remained standing until 1808.