Horn Island, one of the two most stable barriers along the Mississippi-Alabama chain (Cat, East and West Ship, Horn, West Petit Bois, Petit Bois, and Dauphin), provides critical habitat, helps regulate estuarine conditions in the Mississippi Sound, and reduces wave energy and storm surge before they reach the mainland shore. However, important details of the formation and evolution of the island in response to sea-level rise, storms, and antecedent geology remain unclear. This study integrates 2200 km of high-resolution geophysical data, 35 sediment cores, and 18 radiocarbon ages to better understand the geologic history of the island. Incised valleys of the Biloxi and Pascagoula Rivers underlie Horn Island and played a profound role in the evolution of the system. Within the incised valleys, sandy paleochannel deposits represent potential sediment sources during island development. Scour associated with wave and tidal ravinement processes liberated sand from the paleochannels and along with numerous other sizable sand sources on the shelf contributed to the formation and continued maintenance of Horn Island. Based on radiocarbon ages, transgressive ephemeral islands/shoals with no preserved shoreface existed at least 8000 cal yr BP and were frequently overwashed when sea-level rise rates were ~ 4–5 mm/yr. Approximately 5000 cal yr BP, coinciding with a deceleration in sea-level rise to about 1.4 mm/yr and attendant increased sand supply, radiocarbon ages associated with Horn Island's barrier complex and lower shoreface indicate a period of island stabilization. Seismic and sediment core data show a long history of westward lateral migration by longshore currents through tidal ravinement and inlet fill. Subsurface sand packages associated with tidal inlet fill and paleochannels are available for ravinement and may be important sand sources for Horn Island to maintain subaerial exposure with the expected accelerated future sea-level rise.