This study presents a comprehensive spatiotemporal transcriptome dataset of the human brain, generated from 1,340 tissue samples of 57 postmortem human brains, covering embryonic development to late adulthood. The dataset includes 16 brain regions, including the cerebellar cortex, thalamus, striatum, amygdala, hippocampus, and 11 neocortical areas (NCX). The study also includes genotyping of 2.5 million SNPs and assessment of copy number variations. Approximately 86% of protein-coding genes were expressed, with over 90% showing differential regulation across regions and time. The majority of spatiotemporal differences occurred before birth, followed by increased similarity among regional transcriptomes during postnatal life. Genes were organized into functionally distinct co-expression networks, with sex differences in gene expression and exon usage. The study demonstrates how these results can be used to profile gene trajectories associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia, as well as to discover associations between SNPs and spatiotemporal gene expression. The dataset provides a detailed understanding of the transcriptional foundations of human neurodevelopment, including the spatiotemporal dynamics of gene expression, sex differences, and the regulation of alternative exon usage. The study also identifies sex-biased gene expression and exon usage, revealing differences in gene expression between males and females. The results highlight the importance of spatiotemporal gene expression in neurodevelopment and provide insights into the genetic and molecular mechanisms underlying brain development and disease. The study also identifies expression quantitative trait loci (eQTLs) associated with gene expression, demonstrating the role of genetic variation in regulating gene expression. The findings contribute to a better understanding of the complex spatiotemporal dynamics of the human brain transcriptome and the transcriptional mechanisms underlying neurodevelopment and disease.This study presents a comprehensive spatiotemporal transcriptome dataset of the human brain, generated from 1,340 tissue samples of 57 postmortem human brains, covering embryonic development to late adulthood. The dataset includes 16 brain regions, including the cerebellar cortex, thalamus, striatum, amygdala, hippocampus, and 11 neocortical areas (NCX). The study also includes genotyping of 2.5 million SNPs and assessment of copy number variations. Approximately 86% of protein-coding genes were expressed, with over 90% showing differential regulation across regions and time. The majority of spatiotemporal differences occurred before birth, followed by increased similarity among regional transcriptomes during postnatal life. Genes were organized into functionally distinct co-expression networks, with sex differences in gene expression and exon usage. The study demonstrates how these results can be used to profile gene trajectories associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia, as well as to discover associations between SNPs and spatiotemporal gene expression. The dataset provides a detailed understanding of the transcriptional foundations of human neurodevelopment, including the spatiotemporal dynamics of gene expression, sex differences, and the regulation of alternative exon usage. The study also identifies sex-biased gene expression and exon usage, revealing differences in gene expression between males and females. The results highlight the importance of spatiotemporal gene expression in neurodevelopment and provide insights into the genetic and molecular mechanisms underlying brain development and disease. The study also identifies expression quantitative trait loci (eQTLs) associated with gene expression, demonstrating the role of genetic variation in regulating gene expression. The findings contribute to a better understanding of the complex spatiotemporal dynamics of the human brain transcriptome and the transcriptional mechanisms underlying neurodevelopment and disease.