•Abnormal white matter is associated with MDD in adolescents and young adults.•Lower FA mainly located in the corpus callosum and frontal-subcortical circuits.•Impairments of white matter integrity may contribute to the pathogenesis of MDD. Adolescents and young adults are at a critical stage of life development, and depression can have serious consequences. In recent decades, an increasing number of diffusion tensor imaging (DTI) studies of major depressive disorder (MDD) have reported inconsistent alterations in white matter (WM) microarchitecture. To rule out the confounding effects of age, we conducted a meta-analysis of fractional anisotropy (FA) in adolescents and young adults with MDD to identify abnormalities in WM involved in the pathogenesis of MDD using anisotropic effect-size signed differential mapping (AES-SDM). The pooled meta-analysis revealed significantly lower FA mainly in the corpus callosum (CC) extending to the left anterior thalamic projections (ATP) and left cortico-spinal projection (CSP) in depressed adolescents and young adults than that in healthy controls. A reduction in FA was also identified in the right frontal orbito-polar tract (FOPT) extending to the right inferior fronto-occipital fasciculus (IFOF). In the meta-regression analysis, the mean age of patients, percentage of female patients and duration of depression were not linearly associated with abnormalities in FA. These results constitute robust evidence that abnormalities in WM microarchitecture in the interhemispheric connections and frontal-subcortical neuronal circuits may contribute to the pathogenesis of MDD during adolescence and young adulthood.