For the Cherokee, a large part of Gordon County was originally hunting grounds. With the depletion of the game, due to over-hunting by both the Cherokee and settlers, these American Indians looked to the west for better lands. They began to build in the county, including the capital city of their new nation, New Echota. Begun in 1825, the city sees ratification of the Nation's Constitution in 1827 and the first election in 1828. Modeled after the U.S. Constitution, the document creates a bicameral legislature, a chief executive and a Supreme Court. The Cherokee Phoenix is published in the town, on the Oostanaula a few hundred feet from the confluence of the Conasauga and Coosawattee Rivers. A nearby road ran from South Georgia to Tennessee. It was on this road that Joseph Crutchfield built what became known as Oothcalooga or Ougillogy Morovian Mission Station in 1821. This building would serve as a girls school and home to area missionaries including John Gambold until 1833 or 1834.

As settlers move in after the sixth Georgia Land Lottery (1832), the capital gradually becomes a ghost town. Fort New Echota is built in the town to house the Cherokee before moving west on the Trail of Tears.

Gordon County remained agricultural prior to the Civil War, although the Western and Atlantic Railway did stimulate some industry after 1848. During The War Between the States a number of battles were fought in the county, most notably the battle of Resaca, an early struggle during the Atlanta Campaign.

On March 20, 1888 the city of Calhoun, county seat of Gordon County, was destroyed by a tornado. The courthouse suffered serious damage. On October 23, 1888 a fire swept through the city, destroying a significant amount of the remaining buildings. In 1920 the Gordon Women's Club was founded, making it one of the oldest in the state. During the 1940's and 1950's Peacock (or Bedspread) Alley bisected the county.

North Georgia is renown for its legendary educators. Martha Berry and John Jacob Flourney in Walker County and Andrew Richey in Rabun County join Cosby Smith Hubbard as the most famous of these people. Smith, who was born in Calhoun on December 24, 1889 served in both the Georgia House and Senate. During his terms he proposed three landmark pieces of legislation regarding education. The first mandatory seven-month school term, creation of a board of education, and free textbooks for all students. His effective distribution of these textbooks earned him the praise of educators across the nation, and many Southeastern states adopted his "Georgia Plan." He also advocated and oversaw the creation of a rural public library system in the state.