Human SAMD9 and SAMD9L are duplicated genes that encode innate immune proteins restricting poxviruses and lentiviruses, such as human immunodeficiency virus (HIV). Mutations in these genes are implicated in genetic diseases and cancer. Here we combined structural similarity searches, phylogenetics and population genomics with experimental assays of SAMD9/9L functions to resolve the evolutionary and functional dynamics of these immune proteins, spanning from prokaryotes to primates. We discovered structural analogues of SAMD9/9L in the antibacteriophage defence system, Avs, resulting from convergent evolution. Further, the predicted nuclease site was conserved in bacterial analogues and was essential for cell death, suggesting a fundamental role in defence across different life kingdoms. Despite this shared immunity, we identified genomic signatures of evolutionary arms races in mammals, with remarkable gene copy number variations. We further unveiled that the absence of SAMD9 in bonobos corresponds to a recent gene loss still segregating in the population. Finally, we found that chimpanzee and bonobo SAMD9Ls have enhanced anti-HIV-1 functions compared with the human orthologue. These SAMD9/9L adaptations probably resulted from strong viral selective pressures, including by lentiviruses, and could contribute to lentiviral resistance in bonobos. Evolutionary characterization of Avs9 and SAMD9/9L provides a deeper understanding of how the immune system adapts to fight viruses over billions of years of evolution.