To examine trends of Rocky Mountain spotted fever (RMSF) incidence among American Indians compared with other race groups, a retrospective analysis of national RMSF surveillance data reported to the National Electronic Telecommunications System for Surveillance and the Tickborne Rickettsial Disease Case Report Forms system were used. The RMSF incidence for American Indians, which was comparable to those for other race groups during 1990-2000, increased at a disproportionate rate during 2001-2005. The average annual incidence of RMSF reported among American Indians for 2001-2005 was 16.8 per 1,000,000 persons compared with 4.2, 2.6, and 0.5 for white, black, and Asian/Pacific Islander persons, respectively. Most cases in American Indians were reported from Oklahoma (113.1 cases per 1,000,000), North Carolina (60.0), and Arizona (17.2). The incidence of RMSF increased dramatically among American Indians disproportionately to trends for other race groups. Education about tick-borne disease and prevention measures should be addressed for high-risk American Indian populations.