Born in Tennessee to biracial parents of Cherokee and Scottish heritage, she came to Indian Territory on the Trail of Tears.

She graduated in 1855 as valedictorian of the inaugural class of the Cherokee Female Seminary and began teaching at the school the following year.

During her career, which lasted until 1893, she trained numerous Native American leaders, such as Alice Brown Davis, Samuel Houston Mayes, and Thomas Buffington.

[4] In 1833, Jesse became a Baptist preacher and served with Evan Jones as a missionary among the Cherokee and interpreter for other clergy and political leaders of his tribe.

[21] That year, the Cherokee Council authorized the building of male and female seminaries to provide high school education to tribal members.

[22] Both schools were completed in 1850,[23] and Carrie entered the Cherokee Female Seminary in Park Hill as one of its first class of students.

[12][24] In 1858, she was transferred to the rural Muddy Springs School, located in the Flint District of the Cherokee Nation,[12] about three miles from Stilwell.

[26] Her mother, Eliza, still owned one slave when the war broke out, but the Baptist church was involved with the abolition movement.

The educational system was changed to provide instruction in Cherokee with courses in English to assist students in becoming fluent in both languages.

[39] In 1898, the US Congress passed the Curtis Act, forcing the Five Civilized Tribes to distribute tribally held lands as individual allotments of private property.

They asked to be granted the 85 acres which they had fenced and improved in Baptist and the adjacent land in Section 13, Township 18, Range 45.

[51] In 1917, the year that her husband died,[52] an article in the Westville Record, "The History of Education in Adair County", named Quarles as "among the best teachers of her time".

[30] Her biographer, Marilyn Watt wrote, "Carrie Bushyhead Quarles carved a niche for herself in what was perhaps the only accepted outlet for female leadership, teaching.

[54] The play was performed as an outdoor production and staged at the Adams Corner Rural Village on the site of the Heritage Center.

[56][57] The first act of the play featured the character of Quarles retelling her life from the Trail of Tears to the post-Antebellum period.