The Ozarks’ western most region is East Oklahoma. Every year tourists visit this region for both the culture and the outdoor adventures. Eastern Oklahoma’s Cookson Hills are an extension of the Boston Mountains of Arkansas to the east and the southwestern margin of the Ozark Plateau. This mountain range is located between Stilwell, Sallisaw, and Tahlequah. The Cookson Hills are rich in American Indian history. The area became part of the Cherokee Nation in the early 20th century until 1907, when Oklahoma became a state.

The Cookson Hills are in southeastern Cherokee County, the name of the county indicating the group that historically controlled the area and were once included in the Cherokee Nation's Tahlequah District. In the twentieth century the hills were also the home of the notorious, Depression-era bank robber Charles Arthur "Pretty Boy" Floyd.

Tahlequah is a city in Cherokee County, Oklahoma located at the foothills of the Ozark Mountains and is a popular tourist destination. It is part of the Green Country region of Oklahoma and was established as a capital of the 19th-century Cherokee Nation in 1839, as part of the new settlement in Indian Territory after the Cherokee Native Americans were forced west from the American Southeast on the Trail of Tears.

The building that once housed the Supreme Court of the Cherokee has been converted into a museum and is popular with tourists visiting the area. The Cherokee National Supreme Court Museum was constructed on the southeast corner of the town square by James S. Pierce in 1844. The first chief justice of the Cherokee Nation, John Martin (judge) (1784–1840) held court here. The printing press for the early-day Cherokee Phoenix newspaper was also located in this building, and a reproduction of the press and the newsroom can be seen here.

Also, a popular tourist destination for this part of the Ozarks region is the J.T. Nickel Family Nature and Wildlife Preserve, located in Cherokee County, Oklahoma. It is privately owned and managed by the Oklahoma Nature Conservancy. This preserve contains 17,000 acres of forest and grassland. Spring-fed creeks meander through the rugged lands of steep slopes and narrow valleys that harbor oak-hickory forest, lofty pine woodlands, and a diverse mix of savanna, shrubland, and prairie. In recent years, elk have been reintroduced at the Preserve.