Spalding County was created in 1851 by the state legislature from parts of Fayette, Henry, and Pike counties. Forty miles south of downtown Atlanta, and comprising 198 square miles, the county was named for Thomas Spalding, an influential statesman and planter from coastal Georgia.

The incorporated communities in Spalding County are Griffin, Orchard Hill, and Sunny Side. The county seat is Griffin, where the current county courthouse was built in 1985. Griffin was incorporated in 1843, when it was located in Pike County. Known as Pleasant Grove until 1841, the town was first settled in the mid-1820s. In 1840 Lewis Lawrence Griffin, a banker, planter, philanthropist, and the first president of the Macon and Western Railroad, bought 800 acres in the area. He sold off lots in town, with plans to develop the community into an elaborate city with wide boulevards. Pleasant Grove citizens renamed the town to honor him.

Among the interesting sites in the county is the Orr-Williamson-Gaissert Homeplace (also known as the Old Gaissert Homeplace, the Williamson Place, or the Mary Brook Farm), northeast of Williamson. The site won a 2002 Georgia Centennial Farm Award, which honors families and farms for preserving their historic properties. Oak Hill Cemetery, part of Griffin's original city plan, is the burial site of many historical figures associated with Spalding County.

Although it has remained a county of small-town communities, Spalding's proximity to Atlanta has attracted new residents from the city. Several regional facilities, including Spalding Regional Medical Center and Griffin Technical College, also draw people to the area. The University of Georgia College of Agricultural and Environmental Sciences supports a Griffin campus that provides agricultural education, conducts research, maintains an agricultural extension service, and serves the needs of area residents and farmers with information and other assistance.