Before the construction of Fort Johnston, British settlements along the Carolina coast lacked fortifications to protect them against pirates and privateers, and numerous Spanish attackers exploited this weakness.

In response to these attacks, Governor Gabriel Johnston in 1744 appointed a committee to select the best location to construct a fort for the defense of the Cape Fear River region.

Facing increasingly bold Spanish privateer raids, the General Assembly of North Carolina colony in April 1745 authorized the construction of "Johnston's Fort" near the mouth of the Cape Fear River.

Finding none at the time of their raid, the privateers sailed upriver and attacked Brunswick, North Carolina by sea and land, looting the town and taking hostages over two days.

American patriots attacked the home of Josiah Martin, British royal governor of the Province of North Carolina, at New Bern, on 24 April 1775.

Governor Martin then sent his family to New York, transferred his headquarters to Fort Johnston on 2 June 1775, and instigated a plot to arm enslaved persons.

Governor Martin and his supporters removed most military stores, dismounted the cannon of the fort, and fled aboard the British sloop-of-war Cruiser at anchor in the Cape Fear River.

[3] During winter 1775/1776, the British army sent seven regular regiments and two companies of artillery to the lower Cape Fear region, aspiring to rouse Loyalist colonists to take arms to restore Royal Governor Martin to power.

When British Major James Henry Craig entered the region on 25 January 1781, Captain Ellis left Fort Johnston.

Major Craig aimed to establish a supply base for General Charles Cornwallis and probably destroyed the nascent Fort Johnston again.

Governor William Hawkins assigned four militia companies from coastal southern North Carolina to Fort Johnston to strengthen the defenses of Cape Fear during the War of 1812.

Soldiers at Fort Johnston enjoyed cordial relations with the civilian population of Smithville, North Carolina, throughout the antebellum years, making it a desirable posting.

Early in January 1861, a delegation from Wilmington approached Governor John Willis Ellis, seeking his permission to allow seizure of Fort Johnston from the Union forces, but he denied their request.

Early in the American Civil War, Fort Johnston emerged as a center of Confederate States Army recruitment and training.

Fort Johnston also served as a supply depot for the local system of fortifications, storing and distributing vast quantities of military hardware and sustenance.

The Confederacy increasingly depended on blockade runners breaking through the Union Navy lines to maintain trade necessary to sustain the war effort.

The fort and its garrison maintained the security of the Cape Fear River against Union army and naval forces with weapons, munitions, and supplies imported from Europe, Canada, Bermuda, Cuba, and eventually other Caribbean territories.

In late 1864, President Abraham Lincoln, determined to deal a "mortal blow" to the Confederacy, developed a strategy with his military advisors to cease the only significant sustained blockade running activity, that originating from the Cape Fear River outlet.