The Klamath or "Clamitte" tribe of Indians, for which Klamath County was named, has had a presence for 10,000 years. White settlement began in 1846 along the Applegate Immigrant Trail, which precipitated clashes between the two cultures, and led to the Modoc War of 1872. The Legislative Assembly created Klamath County on October 17, 1882, from the western part of Lake County. Linkville, later known as Klamath Falls, was named county seat.

A treaty was signed with the Klamaths on October 14, 1864, which led to the establishment of the Klamath Reservation. At various times over the next 40 years, different individuals of the Modoc tribe were settled within the reservation. Because of the extensive tracts of forest, the Klamaths were very well off as a people until the termination of the reservation by the U.S. government in 1954. As a result, much of the money received as a result of the termination was lost due to squandering, theft or criminal deception, resulting in increased poverty and loss of tribal identity.

A few of the Klamath refused to accept the buyout money, most notably Edison Choloquin (1924 - 2003). Instead of the cash, he insisted on receiving the title to ancestral land along the Sprague River where he lived. On December 5, 1980, the Chiloquin Act was signed into law, giving him title to the properties he wanted.