Before European settlement, the land that is now Grayson was largely traversed and utilized by the Creek and Cherokee Nations. In the late 19th century, the area began to develop as a small agricultural community. Initially known as Tripoli, and later as Berkley, the town was formally incorporated in 1901. It was renamed Grayson at the request of John E. Gray, a prominent local figure, merchant, and the town's postmaster, who also served as its first mayor.
Early economic development in Grayson was spurred by the construction of a railroad spur in 1898—the Loganville and Lawrenceville Railroad—which allowed local farmers to transport cotton and other goods to larger markets. Although the railroad ceased operations and was dismantled in the 1930s, the town remained a quiet, close-knit farming community for decades.
Grayson's modern history is defined by the explosive suburban growth of Gwinnett County that began in the 1980s and 1990s. As the Atlanta metropolitan area expanded eastward, Grayson transitioned rapidly from a rural agricultural town into a thriving, affluent bedroom community. Today, the city retains its historic downtown core while embracing modern suburban developments, diverse demographics, and a strong local identity.