Adolescents living in rural regions of the United States face substantial barriers to accessing mental health services, creating needs for more accessible, nonstigmatizing, briefer interventions. Research suggests that single-session "growth mind-set" interventions (GM-SSIs)-which teach the belief that personal traits are malleable through effort-may reduce internalizing and externalizing problems in adolescents. However, GM-SSIs have not been evaluated among rural youth, and their effects on internalizing and externalizing problems have not been assessed within a single trial, rendering their relative benefits for different problem types unclear. We examined whether a computerized GM-SSI could reduce depressive symptoms, social anxiety symptoms, and conduct problems in female adolescents from rural areas of the United States. Tenth-grade female adolescents (N = 222, M age = 15.2, 38% White, 25% Black, 29% Hispanic) from 4 rural, low-income high schools in the southeastern United States were randomized to receive a 45-min GM-SSI or a computer-based active control program, teaching healthy sexual behaviors. Young women self-reported depression symptoms, social anxiety symptoms, and conduct problem behaviors at baseline and 4-month follow-up. Relative to the female students in the control group, the students receiving the GM-SSI reported modest but significantly greater reductions in depressive symptoms (d= .23) and likelihood of reporting elevated depressive symptoms (d= .29) from baseline to follow-up. GM-SSI effects were nonsignificant for social anxiety symptoms, although a small effect size emerged in the hypothesized direction (d= .21), and nonsignificant for change in conduct problems (d= .01). A free-of-charge 45-min GM-SSI may help reduce internalizing distress, especially depression-but not conduct problems-in rural female adolescents.