The emerging appreciation of misregulated epigenomes in neural developmental disorders implies an indispensable role of epigenetic regulations during brain development. Zinc Finger Myeloid, Nervy, and DEAF-1 (MYND) type containing 8 (ZMYND8) is an epigenetic regulator known to function as a molecular hub coordinating gene regulation events during DNA damage repair, tumorigenesis, and metastasis. Whereas its role in brain development is yet uncharacterized, recently, mutations in ZMYND8 have been linked to a neurodevelopmental syndrome characterized by intellectual disability (ID) and autism spectrum disorders (ASD). To investigate the potential roles of ZMYND8 in the etiology of ID and brain development, we differentiated wild-type (WT) and ZMYND8-deficient iPSCs into brain organoids. Single-cell RNA-seq analysis and immunohistochemistry showed that the WT organoids reproduced the major neuronal cell types and transcriptomic profiles expected in a brain organoid. Strikingly, ZMYND8-deficient organoids, on the other hand, stimulated a “ventral-like” cellular profile, suggesting that ZMYND8-deficiency led to a switch from dorsal to ventral fate in the brain organoids. Our further characterizations revealed that ZMYND8 regulates genes involved in the SHH and Wnt signalling pathways, the balance between which is essential for the dorsal-ventral patterning during brain development. We also uncovered a strong association between ZMYND8-regulated genes and genes affected in ID and ASD, which aligns with the known association between ZMYND8 variants with these two conditions. In conclusion, we uncovered an epigenetic program, the ZMYND8-regulated gene network, essential for the dorsal-ventral patterning in brain development.