Gaines was born on May 1, 1784 in Stokes County, North Carolina, the son of James and Elizabeth (Strother) Gaines, the former a captain in the Revolutionary War and member of the North Carolina convention that ratified the Federal Constitution, and was a brother of Edmund Pendleton Gaines.
The question of Gaines' education is obscure.
At the age of ten, George Gaines removed with his parents to Sullivan County (now Tennessee), where he lived until he was appointed (1805) assistant factor of the government trading house at St. Stephens, in the Alabama part of the Mississippi Territory. He became factor the next year. The reason for his appointment at twenty-one as Indian agent at a strategic place on the Spanish borderland is obscure. Pioneer life was raw in the Tombigbee Valley, and with the inflow of American settlers the Indians became restless and border troubles and trade rivalry with the Spanish grew apace. Friendly relations with the Choctaws and the success of American over Spanish trade (conducted through the powerful John Forbes Company) depended largely upon Gaines. By adroitness, fair dealing, and kindly ministrations to the Choctaws he commanded their esteem and won their trade. Gaines promoted among the Choctaws the idea of removing beyond the Mississippi, and when they were ready to go they insisted on his helping them to select their lands. His services to the pioneers of the Mississippi Territory were inestimable. Gaines's "Reminiscences of Early Times in the Mississippi Territory" is a valuable contribution to pioneer history. In 1819 he resigned the government factorage and in 1822 became a merchant at Demopolis, the site which he had helped the French colonists to select four years previously. He succeeded in business and represented Clarke and Marengo counties in the Alabama Senate from 1825 to 1827. From 1830 to 1856 he was a merchant in Mobile. He prospered in business, helped to promote the Mobile & Ohio Railroad, and for a time was president of the Mobile branch of the state bank. He did not succeed as bank director, nor did more hard-hearted men when there was a mad rush upon the state banks for loans. Gaines retired from business in 1856 and settled on his plantation at State Line, Mississippi. He was elected to the Mississippi legislature in 1861.
Gaines had an influential role in the early history of Alabama and Mississippi. During his long and varied career he was a federal trade agent for the region's Indian tribes, explored the country west of the Mississippi River and supervised the removal of Choctaw Indians. He also served as a state senator, banker, and railroad lobbyist.
About 1812 Gaines was married to his cousin, Ann Gaines of St. Stephens.
