High throughput single-cell omics applied to non-human primate tissue offer a unique opportunity to solve the monumental puzzle of primate brain aging. Here, we profiled the transcriptome and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus monkeys of different ages including exceptionally old ones. We dissect the dynamic molecular events leading to alterations in processes such as synapsis or myelination in a cell- and brain region-specific manner. We also pinpoint deep layer excitatory neurons in the prefrontal cortex and the multicellular networks in the pons and medulla as hotspots for increased vulnerability. Moreover, comparison with datasets from human neurodegeneration demonstrates the existence of both common and unique mechanisms involved in homeostatic loss. In addition, we determine the underlying cascades of transcription factors and identify aging-regulated loci associated with either longevity or neurodegeneration. Our spatiotemporal roadmap constitutes a fundamental resource for understanding primate brain aging.