KDM5B is a histone demethylase implicated in early development, with loss-of-function mutations linked to recessive neurodevelopmental disorders exhibiting variable penetrance. Despite this, its molecular function during early human neurogenesis remains unclear. To address this, we investigated the function of KDM5B in early neuronal differentiation by CRISPR knock-out of KDM5B in human induced pluripotent stem cells (iPSCs). We investigated how loss of KDM5B impacts the transition from pluripotent stem cell down a neural lineage. Differentiation of KDM5B-KO iPSCs revealed a delay in the transition from pluripotent stem cells to neural progenitor cells, with the delay most evident within the first five days of differentiation and associated with changes in embryoid body morphology. Single-cell RNA sequencing and immunofluorescence staining revealed that KDM5B is dispensable for the maintenance of pluripotency but plays a critical role in early neuronal lineage commitment. These findings highlight KDM5B as an important epigenetic regulator in early neuronal development and offer a human-relevant model to study its function. Understanding the mechanisms by which KDM5B regulates neuronal differentiation may provide valuable insights into the pathogenesis of KDM5B-related developmental disorders and guide future therapeutic strategies.