Henry County comprises 323 square miles in the Atlanta metropolitan area south of the city. Named for Revolutionary War (1775-83) patriot and orator Patrick Henry, it was created in May 1821 by the Georgia Land Lottery Act of that year. Enacted four months after the Creeks ceded a large portion of their land in the Treaty of Indian Springs, the act named five new counties, Henry among them.

McDonough, laid out by the state legislature on the site of a prominent Indian trading post, was incorporated on December 17, 1823, as Henry County's seat. It was named in honor of Thomas Macdonough, a naval captain who defeated the British fleet on Lake Champlain during the War of 1812 (1812-15).

In addition to McDonough, Henry County's largest communities are Stockbridge, Hampton, and Locust Grove.

Stockbridge was founded in 1829 when Concord Methodist Church was built near the present town, attracting people who built their homes nearby. It was named after Levi Stockbridge, a noted agriculturalist from Massachusetts. In 1882 the town was relocated a mile south of its first site because the Southern Railroad needed a railroad stop there. Stockbridge was incorporated as a town in 1895 and then as a city in 1920.

Locust Grove was incorporated in 1893; its name is said to have come from a grove of locust trees around the former home of an early resident.  Locust Grove Institute was opened in 1894 by the local Baptist church and Mercer University. Operating as a college preparatory school until its closure in 1930, the institute's buildings now form the Locust Grove Municipal Complex.