The piRNA pathway suppresses transposable elements in germline cells across the animal kingdom. However, despite their essential function for fertility, piRNA pathway genes of animals with diverse active transposon families, such as fruit flies and teleost fish, are known to be rapidly evolving. The functional impact of such rapid evolution of essential genome defence genes remains enigmatic. To address this question, we performed a yeast-two-hybrid screen to systematically test protein-protein interactions of eleven orthologous genes involved in piRNA precursor expression from five Drosophila species. Our data identify several conserved protein-protein interactions not impacted by rapid sequence evolution, but also reveal two types of molecular innovation within the Drosophila piRNA pathway: (1) co-evolution of PPIs as shown by species incompatibilities in protein-protein interactions that are otherwise conserved between orthologs from the same species, and (2) protein interaction rewiring exemplified by the species-specific recruiters of CtBP, a co-factor required to suppress canonical transcription of transposons at Rhino-occupied loci. Combined with evolutionary analyses and complementary protein-protein interactions assays our data uncover how an arms race, such as the one between transposons and the piRNA pathway in Drosophila, can lead to recurrent innovation of conserved protein interaction networks while preserving the pathway's core function.