Amelia Island was home to Timucua-speaking communities long before Europeans entered the region. Spanish expeditions claimed the coast in the sixteenth century, while French Huguenots briefly challenged Spanish power from nearby Fort Caroline. Missions, warfare, disease, slave raiding, and colonial rivalry transformed Indigenous life. Spain named the island Santa María; Britain renamed it Amelia in the eighteenth century. Its deepwater approaches and position near the Georgia border repeatedly made the island valuable to merchants, soldiers, privateers, and smugglers.

During Britain's rule of East Florida from 1763 to 1783, plantations and trade expanded before Spain recovered the province. The town of Fernandina was laid out near Old Town under Spanish authority and named in honor of King Ferdinand VII. In 1811–1812, American-backed Patriots seized the island before United States forces withdrew. Gregor MacGregor's followers, privateers associated with the Green Cross flag, and forces linked to Luis Aury occupied Fernandina in 1817, creating a short-lived succession of regimes.

The United States took formal possession of Florida in 1821. Fernandina shifted southward after Senator David Levy Yulee's Florida Railroad reached the island in the 1850s, connecting the Atlantic to the Gulf coast. The new town developed a regular grid around the rail terminus and harbor. During the Civil War, Confederate forces abandoned Amelia Island in 1862, and United States troops occupied it. The port received soldiers, refugees, formerly enslaved people, military supplies, and wartime shipping.

After the war, lumber, phosphate, fishing, shrimping, rail traffic, and tourism supported the town. Commercial blocks, churches, houses, warehouses, and civic buildings reflected prosperity but also segregation and unequal access to property and work. Fires, hurricanes, economic downturns, and changing transportation threatened older structures. Preservation campaigns in the twentieth century recognized the architectural concentration around Centre Street and helped establish the historic district while adapting buildings for shops, restaurants, lodging, and public use.

The Amelia Island Historic District now preserves a layered port town shaped by Indigenous history, several colonial empires, brief revolutionary governments, railroad development, war, and maritime commerce. Its Victorian appearance is only the most visible layer of a much longer story. Responsible interpretation connects the picturesque streets to Timucua displacement, slavery and emancipation, Black neighborhoods, immigrant labor, and waterfront industry. Preservation depends on maintaining a living community while managing tourism, coastal storms, rising water, redevelopment pressure, and the fragile archaeology of earlier settlements around the island's changing shoreline and harbor approaches today under difficult modern conditions.