Across internally fertilising species, males transfer ejaculate proteins that trigger wide-ranging changes in female behaviour and physiology. Much theory has been developed to explore the drivers of ejaculate protein evolution. The accelerating availability of high-quality genomes now allows us to test how these proteins are evolving at fine taxonomic scales. Here, we use genomes from 264 species to chart the evolutionary history of Sex Peptide (SP), a potent regulator of female post-mating responses inDrosophila melanogaster. We infer thatSPfirst evolved in theDrosophilinaesubfamily and has followed markedly different evolutionary trajectories in different lineages. Outside of theSophophora-Lordiphosa, SPexists largely as a single-copy gene with independent losses in several lineages. Within theSophophora-Lordiphosa, theSPgene family has repeatedly and independently expanded. Up to seven copies, collectively displaying extensive sequence variation, are present in some species. Despite these changes,SPexpression remains restricted to the male reproductive tract. Alongside, we document considerable interspecific variation in the presence and morphology of seminal microcarriers that, despite the critical role SP plays in microcarrier assembly inD. melanogaster, appear to be independent of changes in the presence/absence or sequence of SP. We end by providing evidence that SP’s evolution is decoupled from that of its receptor, SPR, in which we detect no evidence of correlated diversifying selection. Collectively, our work describes the divergent evolutionary trajectories that a novel gene has taken following its origin and finds a surprisingly weak coevolutionary signal between a supposedly sexually antagonistic protein and its receptor.