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Background: Major depressive disorder (MDD) is a leading cause of disability. To understand why depression develops, it is important to distinguish between early neural markers of vulnerability that precede the onset of MDD and features that develop during depression. Recent neuroimaging findings suggest that reduced global and regional intracortical myelination (ICM), especially in the lateral prefrontal cortex, may be associated with depression, but it is unknown whether it is a precursor or a consequence of MDD. The study of offspring of affected parents offers the opportunity to distinguish between precursors and consequences by examining individuals who carry high risk at a time when they have not experienced depression. Methods: We acquired 129 T1-weighted and T2-weighted scans from 56 (25 female) unaffected offspring of parents with depression and 114 scans from 63 (34 female) unaffected offspring of parents without a history of depression (ages 9 to 16 years). To assess scan quality, we calculated test-retest reliability. We used the scan ratios to calculate myelin maps for 68 cortical regions. We analyzed data using mixed-effects modeling. Results: ICM did not differ between high and low familial risk youths in global (B = 0.06, SE = 0.03, p = .06) or regional (B = 0.05, SE = 0.03, p = .08) analyses. Our pediatric sample had high ICM reliability (intraclass correlation coefficient = 0.79; 95% CI, 0.55–0.88). Conclusions: Based on our results, reduced ICM does not appear to be a precursor of MDD. Future studies should examine ICM in familial high-risk youths across a broad developmental period.