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.

[9][10] It was established in 1828—in land that was part of 1816's Lovely Donations, becoming the first Cherokee Nation–West capital city.

At that time, Takatoka briefly became the Nation's capital during the construction of the capitol building at Tahlequah.

The town site of 160 acres (65 ha) was surveyed in 1843, and in the same year an intertribal council attracted ten thousand participants representing 21 different tribes.

In 1844 the National Hotel was built, and the newspaper Cherokee Advocate issued its first edition using a printing press installed in the brand-new Supreme Court building.

Scholars report the Cherokee word 'di li gwa' describes a type of native grain with a red hue that grew in the flat open areas of east Tennessee.

The idea that 'tahlequah' means 'plains' lends weight to the belief that the name refers to the wide open grassy areas of Great Tellico.

Local legend states the name is derived from Cherokee words 'ta-li' and 'ye-li-quu' meaning 'just two' or 'two is enough'.

Supposedly three tribal elders had planned to meet to determine the location of the Cherokee Nation's permanent capital.

Most of these buildings were destroyed during the Civil War, during which the Cherokee became divided into two bitterly opposing sides.

In 1907, at the time of Oklahoma statehood, the building was converted into the Cherokee County courthouse.

The Cherokee Female Seminary, which had originally been constructed in Park Hill, burned in 1887, and was rebuilt in Tahlequah.

Tahlequah, like most of the Southern United States, has a humid subtropical climate (Köppen Cfa) with uncomfortably hot and humid summers, generally warm but very variable springs and autumns, and cool winters with frequent frosts and occasional spells of severe weather dominated by cold, dry Canadian air.

The following schools have Tahlequah postal addresses but are in the Park Hill census-designated place.

[23] Tahlequah is home to the capital of the Cherokee Nation of Oklahoma and about 25 percent of the students at NSU identify themselves as American Indian.

[24] The university has many courses focused on Native American linguistics, and offers Cherokee language Education as a major.

The first chief justice of the Cherokee Nation, John Martin held court here.