When the American Revolution was over, Fort Moultrie was neglected and by 1791, little of it remained. Then, in 1793, war broke out between England and France. The next year Congress, seeking to safeguard American shores, authorized the first system of nationwide coastal fortifications. A second Fort Moultrie, one of 20 new forts along the Atlantic Coast, was completed in 1798. It too suffered from neglect and was finally destroyed by a hurricane in 1804. By 1807 many of the other First System fortifications were in need of extensive repair. Congress responded by authorizing funds for a Second System, which included a third Fort Moultrie. By 1809 a new brick fort stood on Sullivan’s Island.

Between 1809 and 1860 Fort Moultrie changed little. The parapet was altered and the armament modernized, but the big improvement in Charleston's defenses during this period was the construction of Fort Sumter at the entrance of the harbor. The forts ringing Charleston Harbor – Forts Moultrie, Sumter, Johnson, and Castle Pinckney -- were meant to complement each other, but, ironically they received their first shots as opponents.

In December, 1860 South Carolina seceded from the Union, and the Federal garrison abandoned Fort Moultrie for the stronger Fort Sumter. Three and a half months later, Confederate troops shelled Sumter into submission, plunging the nation into Civil War. In April, 1863 Federal ironclads and shore batteries began a 20-month bombardment of Forts Sumter and Moultrie, yet Charleston's defenses held. When the Confederate army evacuated the city in February, 1865, Fort Sumter was little more than a pile of rubble and Fort Moultrie lay hidden under the bank of sand that protected its walls from Federal shells. The new rifled cannon used during the Civil War had demolished the brick-walled fortifications.

Fort Moultrie was modernized in the 1870s, employing concepts developed during the war. Huge new cannon were installed, and magazines and bombproofs were built of thick concrete, then buried under tons of earth to absorb the explosion of heavy shells. In 1885, President Grover Cleveland appointed Secretary of War William C. Endicott to head a board to review the coastal defenses of the United States and recommend how they might be improved in light of newly developing weapons technology. The system that emerged, named for Endicott, again modernized the nation’s fortifications. New batteries of concrete and steel were constructed in Fort Moultrie. Larger weapons were emplaced elsewhere on Sullivan’s Island, and the old fort became just a small part of the Fort Moultrie reservation that covered much of the island.

As technology changed, harbor defense became more complex. The world wars brought new threats of submarine and aerial attack and required new means of defense at Moultrie. Yet these armaments also became obsolete as nuclear weapons and guided missiles altered the entire concept of national defense.