Background: Elevated rate of aging-related biological and functional decline, termed “accelerated aging,” is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods: The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20–60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20–79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Results: Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ ( p = .04) but not the MDD ( p = .80) cohort. Diagnosis-by-age interaction was nominally significant ( p