Mutations in Zinc Finger Myeloid, Nervy, and DEAF-1 (MYND) type containing 8 (ZMYND8) have recently been linked to a neurodevelopmental syndrome characterised by intellectual disability (ID) and cardiac abnormalities. While ZMYND8 is known to play transcriptional regulatory roles in immune cells and cancer cells, its role in the brain is yet uncharacterised. To investigate the potential roles of ZMYND8 in the aetiology of ID and brain development, we assessed the effects of ZMYND8 knock-out (KO) on gene expression and brain organoid development. In line with the known role of ZMYND8 as a molecular hub coordinating regulatory events in transcriptional and epigenetic networks, we observed widespread changes in gene expressions in ZMYND8 KO iPSCs. In brain organoids generated by directed differentiation to dorsal forebrain, ZMYND8 KO led to impaired organoid development, with loss of the layered structure observed in wild-type cortical spheroids. scRNA-seq of early-stage organoids uncovered increased expression of neuronal differentiation markers, and reduced expression of neural progenitor marker genes. Overall these data indicate that ZMYND8 is critical for brain development, playing a key role in orchestrating gene expression required for neuronal differentiation and cortex formation.