The Mocama, a Timucua-speaking people, originally occupied the lands in what is now Brunswick. The Spanish established missions in Timucuan villages beginning in 1568. During this time, much of the Native American population was depleted through enslavement and disease. When the Province of Carolina was founded in 1663, the British claimed all lands south to the 31st parallel north, but little colonization occurred south of the Altamaha River as the Spanish also claimed this land. Three years after the Province of Georgia was founded in 1733, James Oglethorpe had the town of Frederica built on St. Simons Island, challenging Spaniards who laid claim to the island. The Spanish were driven out of the province after British victories in the battles of Bloody Marsh and Gully Hole Creek in 1742; it was not until the Treaty of Paris of 1763 that Spain's threat to the province was formally ended, when all lands north of the St. Marys River and south of the Savannah River were designated as Georgia.
The area's first European settler, Mark Carr, arrived in 1738. Carr, a Scotsman, was a captain in Oglethorpe's Marine Boat Company. Upon landing, he established his 1,000-acre (400 ha) tobacco plantation, which he called "Plug Point", along the East and Brunswick rivers. The Province of Georgia purchased Carr’s fields in 1771 and laid out the town of Brunswick in the grid plan akin to that of Savannah, with large, public squares at given intervals. The town was named for the duchy of Brunswick-Lüneburg in Germany, the ancestral home of George III and the House of Hanover. Brunswick was a rectangular tract of land consisting of 383.5 acres (155.2 ha). The first lot was granted on June 30, 1772; 179 lots were granted in the first three years. However, about this time Brunswick lost most of its citizens, many of whom were Loyalists, to East Florida, the Caribbean Basin, and the United Kingdom for protection during the American Revolutionary War. From 1783 to 1788 a number