We sequenced the transcriptomes of 126,840 cells from the prenatal and adult human hypothalamus, revealing a temporal trajectory from proliferative stem cell populations to mature neurons and glia. Developing hypothalamic neurons followed branching trajectories ultimately leading to 370 transcriptionally distinct neuronal subtypes in eleven hypothalamic nuclei in the adult. The uniqueness of hypothalamic neuronal lineages was examined developmentally by comparing excitatory lineages present in cortex and inhibitory lineages in ganglionic eminence, revealing both distinct and shared drivers of neuronal maturation across the human forebrain. Cross-species comparisons to the mouse hypothalamus identified corresponding populations for most neuronal subtypes. However, homologous neuronal subtypes in human vs. mouse expressed unique combinations of transcription factors, suggesting evolutionary differences in gene regulation. These results provide a comprehensive transcriptomic view of human hypothalamus development through gestation and adulthood at cellular resolution.