Born on the Navajo reservation, to Eugene Tapahonso (Bitter Water clan), and Lucille Tapahonso, (Salt Water clan), Luci Tapahonso was raised in a traditional way along with 11 siblings. English was not spoken on the family farm, and Tapahonso learnt it as a second tongue after her native Diné bizaad. Following schooling at Navajo Methodist School in Farmington, New Mexico, and Shiprock High School, she began studies at the University of New Mexico. There she first met Leslie Marmon Silko, the novelist and poet, who was on the faculty staff and who proved to be an important influence on Tapahonso's early writing. In 1982, Tapahonso gained her MA, and she has gone on to teach, first at New Mexico and later at the University of Kansas and now at the University of Arizona.

Her first collection of poetry, assembled when she was still an undergraduate, was published in 1981, but did not make much impact. Following Silko's lead, Tapahonso's early work is often mystical and places much importance on the idea of the feminine as a source of power and balance in the world. She also frequently uses her family and childhood friends in her poetry. Several more collections followed, as well as many individual poems which have been anthologised in others' collections, activist literature, and writing in magazines.

Her 1993 collection Saánii Dahataal (the women are singing), written in Diné and English, was the first to gain her an international reputation, a reputation then cemented by 1997's blue horses rush in.

Tapahonso's writing, unlike that of most Native American writers, is a translation from original work she has created in her tribe's native tongue. Her Diné work includes original songs and chants designed for performance. For this reason, her English work is strongly rhythmic and uses syntactical structures unusual in English language poetry.