In 1699, the Mississippi Gulf Coast became the colonial capital of a European empire when French ships appeared on the horizon. The calm waters of the Mississippi Sound and a natural harbor near Ship Island attracted these early French explorers, who were searching for the mouth of the Mississippi River. The anchorage of these first ships in Mississippi waters marked the birth of France's Louisiana colony, which spread to encompass much of the area that was to become the southeastern United States and to include major cities such as Mobile and New Orleans.

This colonial episode also marked the first sustained contact between the French and the native inhabitants of Mississippi, an event that would have profound consequences for both groups. The French built a fort and founded a settlement on Biloxi Bay that makes this area one of the oldest, continuously occupied communities in the nation. The French settlement at Biloxi Bay that briefly served as the colony's capital and the harbor at Ship Island in the Mississippi Sound served as the entry points for people moving to or through the area, as free colonists, indentured servants or African slaves.

The Mississippi Gulf Coast was part of three colonial empires--those of France, Britain, and Spain--before becoming part of the United States in the early 1800s. It was not long before the waterways of the Mississippi Gulf Coast were witness to important events in the history of this new country.

In 1814, during the War of 1812, the Mississippi Sound was taken over by what has been called the largest amphibious invasion force ever to enter American waters. Dozens of British warships occupied the Sound and thousands of British soldiers encamped on Ship Island in preparation for an attack on New Orleans. While the British were amassing off the coast, Andrew Jackson marched the American army overland across south Mississippi to defend New Orleans. Legend has it that the British arrested a local Frenchman living on Cat Island to conscript him as a guide through the tricky passes of the Mississippi Sound and the marshes of Louisiana that led to the Mississippi River. His refusal, along with a brief naval battle between the British and the Americans in the Mississippi Sound, supposedly delayed the British forces long enough for Jackson to entrench his army and stop the invasion at the Battle of New Orleans.

Ship Island and the Mississippi Gulf Coast again saw military action during the Civil War. In 1859, to provide protection of the shipping lanes and the naturally deep-water anchorage at Ship Island, the U. S. Army Corps of Engineers began building a brick fort on Ship Island that was part of the United States' Third System of coastal fortifications. Ship Island served as a staging ground for ships and thousands of troops before the Union attack on New Orleans in 1862, and later in 1864, before the attack on Mobile Bay. Ship Island was also used during the war as a prison for captured Confederate soldiers and as a detention center for Confederate sympathizers from New Orleans.

During the Civil War, Union troops stationed on Ship Island included the Louisiana Native Guards, African-American militia units composed of freeman of color and former slaves. The 2nd regiment of the Native Guards met Confederates in the battle in Pascagoula and consequently, became the first African-American unit on the Gulf Coast to suffer and inflict causalities.