Spanish expeditions moved through the region from the mid-1500s through the 1660s, the most notable of which was Hernando de Soto's expedition in 1540.His party's documentation of various Indian chiefdoms provides some of the best descriptions about native life in Georgia prior to the eighteenth century.

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After the Trustees lifted the ban on slavery in the colony, Georgians moved quickly to establish a coastal plantation economy based on rice and Sea Island cotton.

It was in Georgia that perhaps the most fateful development for the future of American slavery and the southern economy occurred in 1793, with Eli Whitney's invention of the cotton gin during a visit to the plantation of Catharine Greene, the widow of military leader Nathanael Greene.

The Spanish presence also included Catholic missionaries, who established Santa Catalina de Guale and other short-lived missions at points along Georgia's coast from 1568 through 1684.

These missions played a key role in assimilating the Native American populations of the region into the colonial system.

Another notable first was Along with Alabama and Mississippi, Georgia was home to a significant Native American populace for much longer than any other state along the eastern seaboard.

While white Georgians were not alone in their conflicts with and ultimate removal of that native presence (in Georgia's case, of the Creeks and the Cherokees), the tragic circumstances of the Cherokees' forced exile from the state's northwestern territory in 1838-39, known as the "Trail of Tears," became a particularly potent symbol of the trauma and suffering that all such removals entailed. The construction of railroads connecting Athens, Augusta, Macon, and Savannah was another important development in Georgia during the 1830s.

(Only Virginia was larger, until its northwestern counties withdrew to form the separate state of West Virginia in 1863.) As both an Atlantic seaboard state and a Deep South state, Georgia played a particularly crucial role in the secession crisis and the formation of the Confederacy.

It had the largest population and the largest number of both slaves and slaveholders of any Deep South state (and was second only to Virginia overall), and yet it had two vast geographical areas in which slavery played only a minimal part—the southeastern wiregrass and longleaf pine woods region, and the northern mountains.

Georgia became the fifth state to secede from the Union, on January 19, 1861, yet the state's geographical diversity and the dominance of its nonslaveholding white populace made its selection of delegates to the 1861 secession convention one of the most divided (in terms of delegates for and against secession) within the first wave of southern states to leave the Union.