School-age children frequently present with mental health (MH) problems in school, affecting their academic experience and outcomes. However, school staff report difficulty in identifying and managing such problems. We aimed to determine whether a mental health literacy (MHL) intervention was effective at improving MHL for staff in an urban, predominately Latinx elementary school. A pre/post quasi-experimental design was used. A 20-week MHL intervention that is comprehensive (i.e., not disorder specific) and tiered (i.e., universal as well as targeted services for those with greater needs) was provided as part of an existing school-based mental health prevention and promotion program. A survey adapted from validated measures of MH knowledge and attitudes (including self-efficacy and stigma), as well as use of student support services, was simultaneously administered to staff at the intervention school and a matched comparison school before and after the intervention. Linear and logistic regressions assessed whether changes in MHL and rates of MH referrals varied by school. After controlling for pre-intervention scores, staff in the intervention school had significantly higher knowledge scores (data), higher self-efficacy scores (data), and lower stigma scores (data) in the post-intervention period compared to the comparison school. Following the intervention, more staff in the intervention school reported utilizing student supports to discuss student needs (OR 5.8, 95% CI 2.3–14.6). This intervention, which utilizes a social–ecological framework and tiered approach, led to improvements in MHL of school staff, which may facilitate staff ability to identify and support students’ MH needs.