Brigham Young established the Southern Indian Mission during the October 1853 General Conference. He called several men to go and preach to the native American tribes located in the region known today as southern Utah. Rufus C. Allen was called as their leader. 

These missionaries preached to Native American tribes in the area: Hopi, Navajo, Paiute and Mojave among others. Often the missionaries would not stay long, sometimes only leaving two missionaries with the tribes to continue teaching them.

A settlement mission called the Southern Utah Mission shared the same boundaries as this mission, which also included the "Muddy Mission."