The first Episcopal service was conducted in Fort Defiance in 1889 by Bishop John Miles Kendrick. Intermittent Episcopal mission efforts continued until 1894 when Miss Eliza Thackara accepted the appointment as superintendent of a hospital mission at Fort Defiance. The hospital, the first serving the Navajo, was completed in 1897. When the BIA (Bureau of Indian Affairs) built a hospital the Good Shepherd Hospital specialized in treating trachoma and eventually became an orphanage and boarding school for rural students attending the public schools. The building still stands and now serves the community as The Rev. Margaret Hardy Parish Hall.

The first separate church building was completed in 1908. It was replaced in 1955 for structural and space reasons by a church which is an architectural gem. Designed by the renowned southwest architect, John Gah Meem, whose works surround the Santa Fe Plaza, the church incorporates Navajo craftsmanship and symbolism. Services are conducted in both Navajo and English and seek to honor the richness of the Dine' (Navajo) religious traditions.

The mission compound covers 48 acres and has more than a dozen buildings which presently house artists' studios, offices, a nursing training program, social service programs, a greenhouse/gardening  program, residence and meeting facilities as well as the Hummingbird Gallery and Hozho'  Retreat Center, a retreat/pilgrimage center which can house up to 16 individuals.