Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal, with few simultaneous analyses of multiple brain features across different GDDs. Here, through multimodal neuroimaging of 3 aneuploidy syndromes (XXY total n = 191, 92 control participants, XYY total n = 81, 47 control participants, and trisomy 21 total n = 69, 41 control participants), we systematically mapped the effects of supernumerary X, Y, and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging–derived phenotypes (IDPs). The results revealed considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps revealed highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all 3 GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures. Use of multimodal neuroimaging data in 3 aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality that is being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.