Background: The literature has documented theoretical/conceptual models delineating the facilitating role of peer relationships in academic and non-academic outcomes. However, the mechanisms through which peer relationships link to those outcomes is an area requiring further research. Aims: The study examined the role of adolescents' perceptions of their relationships with same-sex and opposite-sex peers in predicting their academic performance and general self-esteem and the potentially mediating role of school engagement in linking these perceived peer relationships with academic and non-academic outcomes. Sample: The sample comprised 1,436 high-school students (670 boys, 756 girls; 711 early adolescents, 723 later adolescents). Method: Self-report measures and objective achievement tests were used. Structural equation modelling (SEM) was performed to test the hypothesized model and its invariance across gender and age groups. Results: Perceived same-sex peer relationships yielded positive direct and indirect links with academic performance and general self-esteem. Perceived opposite-sex peer relationships yielded positive direct and indirect links with general self-esteem and an indirect positive link with academic performance, but mediation "via" school engagement was not as strong as that of perceived same-sex peer relationships. These findings generalized across gender and age groups. Conclusion: Adolescents' same-sex and opposite-sex peer relationships seem to positively impact their academic performance and general self-esteem in distinct ways. It appears that school engagement plays an important role in mediating these peer relationship effects, particularly those of same-sex peer relationships, on academic and non-academic functioning. Implications for psycho-educational theory, measurement, and practice are discussed.