Microbial communities are complex living networks where bacteria, archaea, and their viruses coexist in dynamic equilibrium. The co-evolution dynamics of the “arms race” between microbes and their phages has led to an incredible diversification of defence biomolecules in microbes. Recent mining efforts of the microbial antiphage arsenal uncovered hundreds of novel defence systems, including Azaca, a 3-protein defence module harbouring a DUF6361-containing protein, a predicted helicase, and a predicted PLD-like nuclease1. The molecular mechanism by which Azaca protects against phages remains unknown. Here, we show that Azaca defence systems are diverse and that the three core genes, ZacABC, likely interact as a trimer featuring conserved pockets consistent with helicase and nuclease cores. Phage challenge assays showed that Azaca grants exceptional defence when recombinantly expressed in E. coli, with a mechanism of immunity that is non-abortive. Structure-guided mutational analysis revealed that the helicase core is both necessary and sufficient for defence while perturbing the PLD-like nuclease active site subtly affects defence. Finally, we describe purification of the trimeric Azaca and experiments towards unravelling the molecular mechanism of Azaca-mediated defence. Thoroughly exploring the structure and function of novel microbial defence systems like Azaca is critical to expanding the range of biotech tools available in molecular science.