Down syndrome is a common neurodevelopmental condition and major genetic cause of intellectual disability. Although trisomy of chromosome 21 is long known as underlying cause, it is not well understood how the increased dosage of over 300 genes on chromosome 21 perturbs transcriptional and epigenetic programmes underlying neural differentiation, and effective therapies are lacking. Mouse models have suggested potential underlying mechanisms, but it is unclear to what extent these are recapitulated in the human brain.Here, we use single cell transcriptomics and epigenomics to generate an atlas of human cortical development in Down syndrome, profiling over 30 foetal brain samples covering post-conceptional weeks 10-20, a key developmental period encompassing cortical neurogenesis, as well as early stages of gliogenesis and neuronal maturation. Preliminary analyses of transcriptional networks in this dataset suggest that the increased activity of a subset of chromosome 21 gene in neural progenitors drives subtle transcriptional and epigenetic alterations and alters signalling responses, leading to the excessive activation of both neuronal and glial differentiation programmes. This may result in precocious and aberrant neural and glial differentiation at the expense of progenitor maintenance, ultimately resulting in early progenitor exhaustion, reduced generation of aberrantly differentiated neural cells and network dysfunction.Overall, our work provides a valuable resource for Down syndrome research and suggests novel mechanisms altering fate choices of neural progenitors, which may indicate new strategies to ameliorate cognitive impairments in this common neurodevelopmental condition.