This study reports the generation and analysis of a comprehensive genome-wide exon-level transcriptome dataset from 16 brain regions across 57 postmortem human brains, spanning from embryonic development to late adulthood. The dataset includes 1,340 tissue samples from both hemispheres of the brain, representing males and females of multiple ethnicities. Approximately 86% of protein-coding genes were found to be expressed, with over 90% showing differential regulation at the transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occurred before birth, followed by an increase in similarity among regional transcriptomes during postnatal development. The study also identified functionally distinct co-expression networks and sex differences in gene expression and exon usage. The findings provide insights into the transcriptional foundations of human neurodevelopment and can be used to profile trajectories of genes associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia. Additionally, the dataset allows for the discovery of associations between SNPs and spatiotemporal gene expression, contributing to a better understanding of inter-individual differences and genetic control of the brain transcriptome.This study reports the generation and analysis of a comprehensive genome-wide exon-level transcriptome dataset from 16 brain regions across 57 postmortem human brains, spanning from embryonic development to late adulthood. The dataset includes 1,340 tissue samples from both hemispheres of the brain, representing males and females of multiple ethnicities. Approximately 86% of protein-coding genes were found to be expressed, with over 90% showing differential regulation at the transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occurred before birth, followed by an increase in similarity among regional transcriptomes during postnatal development. The study also identified functionally distinct co-expression networks and sex differences in gene expression and exon usage. The findings provide insights into the transcriptional foundations of human neurodevelopment and can be used to profile trajectories of genes associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia. Additionally, the dataset allows for the discovery of associations between SNPs and spatiotemporal gene expression, contributing to a better understanding of inter-individual differences and genetic control of the brain transcriptome.