INTRODUCTION: Evidence from previous genetic and post-mortem studies suggested that the myelination abnormality contributed to the pathogenesis of major depressive disorder (MDD). However, image-level alterations in cortical myelin content associated with MDD are still unclear. METHODS: The high-resolution T1-weighted (T1w) and T2-weighted (T2w) brain 3D structural images were obtained from 52 MDD patients and 52 healthy controls (HC). We calculated the vertex-based T1w/T2w ratio using the HCP structural pipelines to characterize individual cortical myelin maps at the fs_LR 32 k surface. We attempted to detect the clusters with significant differences in cortical myelin content between MDD and HC groups. We correlated the cluster-wise averaged myelin value and the clinical performances in MDD patients. RESULTS: The MDD patients showed significantly lower cortical myelin content in the cluster involving the left insula, orbitofrontal cortex, superior temporal cortex, transverse temporal gyrus, inferior frontal cortex, superior frontal gyrus, anterior cingulate cortex, precentral cortex, and postcentral cortex. The correlation analysis showed a significantly positive correlation between the cluster-wise cortical myelin content and the onset age of MDD patients. CONCLUSION: The MDD patients showed lower cortical myelin content in regions of the default mode network regions and salience network than healthy controls.