This suggests that the people later known as Cherokee were once part of the Iroquois and that probably as a result of defeat in warfare moved to the southern Appalachian area. The Encyclopaedia Britanica says that the Cherokee lived around the Great Lakes before their migration to Southern Appalachia. Another source identifies the Iroquois as having migrated from the lower Midwest. This means that the Cherokees could have separated from the other Iroquois by branching off to the east as the main body migrated to the northeast.

One of the possible derivations of the word Cherokee is from a Creek phrase meaning people who speak a different language. This would be a very natural designation for a people who migrated into a region from so far away that their language was unfamiliar. Linguistics has a method for getting an approximate dating of the length of time two languages have been separated and developing independently. It is based upon the number of cognate words in the two languages among a core vocabulary of about two hundred words. This method, called glottochronology, gives an estimate of 6 thousand years for the time of separation between the Cherokee language and the other Iroquois languages. Glottochronology is subject to a high margin of error and many doubt its validity at all.

The Cherokee become part of recorded history with the contact made with the tribe by the De Soto expedition in the sixteenth century. Although the De Soto expedition was Spanish its was recorded in Portuguese by a Portuguese member of the expedition, known only as the Gentleman from Elva. This man transcribed the name of the tribe as Tsalagi and this evolved into Cherokee.

The Cherokee were a hunting and gathering people with a matrilineal family structure. The women grew corn, squash and sweet potatoes. There were seven clans in the tribe and young people had to marry outside of their clan. Because of the matrilineal family structure inheritance was based upon the mother of a child so there was no discrimination against children born into the tribe from non-Cherokee fathers.

In 1715 the Governor of South Carolina estimated the population of Cherokees as somewhat over ten thousand in 30 villages. In 1721 another Governor of South Carolina made a treaty with the Cherokees which established a boundary between Cherokee territory and the colonists. In 1738 an epidemic broke out among the Cherokees which killed about half the population.

In the period after 1756 the Cherokees were involved in the wars between the British and the French as well as wars with other tribes. There were also dissensions developing among the geographic groups of Cherokees, who were divided into the Upper Towns, the Middle Towns and the Lower Towns.

The historic Cherokee territories included what is now northern Georgia, eastern Tennessee, western North and South Carolina. In addition, Cherokees made frequent hunting expeditions into what is now Kentucky and even Ohio.

In the Treaty of Augusta in 1773 the Cherokee leaders gave up claim to two million acres in Georgia and in 1775 a subtribe of the Cherokees in the Treaty of Sycamore Shoals sold their claim to a large tract of land in central Kentucky. Though it is not clear that the Cherokee had any recognized claim to the land in Kentucky a land company used this sale as the basis for taking over that land.

At the beginning of the American Revolution the Cherokee announced their support for the British authorities. The Cherokee launched unsuccessful raids on American settlements and in the subsequent victories by the Revolutionary force the Cherokee had to sue for peace under conditions in which they gave up claims to their lands in North and South Carolina. These cessation of claims were written into the Treaty of DeWitts Corner in 1777 and in the first and second Treaties of Long Island of Holston in 1777 and 1781.

After the defeats Cherokees concentrated on assimilating American technology and culture. They began to farm and live in European style houses. One Cherokee of mixed ancestry George Guess, generally known to history as Sequoyah, developed a syllabary for writing the Cherokee language. A Cherokee newspaper, the Cherokee Phoenix, was started in Georgia in 1828.

Gold was discovered in Cherokee territory in Georgia and American settlers started coming in. Georgia in 1835 struck a treaty with some Cherokees with no official status in which all Cherokee land east of the Mississippi was relinquished for $5 million. The Cherokee people were outraged and the case was fought to the U.S. Supreme Court where the Cherokees won. President Jackson said that Justice Marshall had rendered his vertict, "Now let him enforce it!"

The Cherokees were rounded up by the U.S. Army (under Winfield Scott), their homes were destroyed and they were marched to the area that is now Oklahoma. It is called the Trail of Tears because of the high mortality over the 116 day journey. Approximately one out of four died during the journey. Those who signed the treating in Georgia were assassinated in Oklahoma.

During the Civil War there were Cherokees supporting both sides but the preponderance of the support was for the Confederacy.

The Cherokees are an organized tribe still with official tribal government. They constitute one of the largest of the tribes. There are also an enormous number of Americans who are part Cherokee and probably when a proportional account is taken of the part-Cherokees the Cherokees would be the largest of the tribes.