Annona cherimola (cherimoya) is a species renowned for its delectable fruit and medicinal properties. In this study, we developed a chromosome-level genome assembly for the cherimoya 'Booth' cultivar from the United States. The genome assembly has a size of 794 Mb with a N50 = 97.59 Mb. The seven longest scaffolds account for 87.6% of the total genome length, which corresponds to the seven pseudo-chromosomes. A total of 45,272 protein-coding genes (≥30 aa) were predicted with 92.9% gene content completeness. No recent whole genome duplications were identified by an intra-genome collinearity analysis. Phylogenetic analysis supports that eudicots and magnoliids are more closely related to each other than to monocots. Moreover, the Magnoliales was found to be more closely related to the Laurales than the Piperales. Genome comparison revealed that the 'Booth' cultivar has 200 Mb less repeats than the Spanish cultivar 'Fino de Jete', despite their highly similar (>99%) genome sequence identity and collinearity. These two cultivars were diverged during the early Pleistocene (1.93 Mya), which suggests a different origin and domestication of the cherimoya. Terpene/terpenoid metabolism functions were found to be enriched in Magnoliales, while TNL (Toll/Interleukin-1-NBS-LRR) disease resistance gene has been lost in Magnoliales during evolution. We have also identified a gene cluster that is potentially responsible for the biosynthesis of acetogenins, a class of natural products found exclusively in Annonaceae. The cherimoya genome provides an invaluable resource for supporting characterization, conservation, and utilization of Annona genetic resources.