Santa Fe is an unincorporated community in southeastern Monroe County, Missouri, United States. It is located about twenty-five miles north of Mexico, Missouri near the southern edge of Mark Twain Lake. The Clemens family (of which was Samuel Clemens, aka "Mark Twain") owned several tracts of land in the area. It was settled in 1837 and named for Santa Fe, New Mexico. It was previously incorporated, but was disincorporated in 1950.