Background.High rates of mental illness and addictions are well documented among youth in Nicaragua. Limited mental health services, poor mental health knowledge and stigma reduce help-seeking. The Mental Health Curriculum (MHC) is a Canadian school-based program that has shown a positive impact on such contributing factors. This pilot project evaluated the impact of the MHC on mental wellness and functioning among youth in Leon, Nicaragua.Methods.High school and university students (aged 14–25 years) were assigned to intervention (12-week MHC; n = 567) and control (wait-list; n = 346) groups in a non-randomized design. Both groups completed measures of mental health knowledge, stigma and function at baseline and 12 weeks. Multivariate analyses and repeated measures analyses were used to compare group outcomes.Results.At baseline, intervention students showed higher substance use (mean difference [MD] = 0.24) and lower perceived stress (MD = −1.36) than controls (p < 0.05); there were no other group differences in function. At 12 weeks, controlling for baseline differences, intervention students reported significantly higher mental health knowledge (MD = 1.75), lower stigma (MD = 1.78), more adaptive coping (MD = 0.82), better lifestyle choices (MD = 0.06) and lower perceived stress (MD = −1.63) (p < 0.05) than controls. The clinical significance as measured by effect sizes was moderate for mental health knowledge, small to moderate for stigma and modest for the other variables. Substance use also decreased among intervention students to similar levels as controls (MD = 0.03) (p > 0.05).Conclusions.This pilot investigation demonstrates the benefits of the MHC in a low-and-middle-income youth population. The findings replicate results found in Canadian student populations and support its cross-cultural applicability.