Communication with sexual partners about protection against sexually transmitted infections (STIs) is associated with safer sexual behaviors among general populations of youth, but little is known about partner communication among American Indian youth. We assessed the prevalence of adolescents’ communication with sexual partners about STI prevention and used multivariable logistic regression to examine associations between communication and safer sexual behaviors (condom use, reliable contraceptive use, and dual method use) among a statewide sample of in-school, American Indian youth in Minnesota in 2013 and 2016 (n = 739). Half (49.5%) of sexually experienced American Indian youth reported talking about STI prevention at least once with every sexual partner. Communication was associated with all examined safer sexual behaviors among females and only with condom use among males. Study findings highlight the importance of school nurses, health educators, and other clinicians addressing partner communication when counseling adolescent patients.