Predatory interactions among microbes are a major evolutionary driving force for biodiversity. The fungivorous amoeba Protostelium aurantium has a wide fungal food spectrum including major pathogenic members of the genus Candida. Phagocytic feeding by P. aurantium is highly effective with C. parapsilosis, a major pathogenic yeast. Here we show that upon ingestion by the amoeba C. parapsilosis is confronted with an oxidative burst and undergoes phagosomal lysis within minutes. On the fungal side, a functional genomic approach identified the fungal copper and redox homeostasis as primary targets of amoeba predation with the highly expressed copper exporter Crp1 and the peroxiredoxin Prx1 contributing to survival when encountering P. aurantium. The fungolytic activity was largely retained in intracellular vesicles of the amoebae. Following their isolation, the content of these vesicles induced immediate killing and lysis of C. parapsilosis. A proteomic analyses identified 56 vesicular proteins. Although fully unknown proteins were dominant, many of them could be categorized as hydrolytic enzymes presumably targeting the fungal cell wall, indicating that fungal cell wall structures are under predatory selection pressure in natural environments.