The human fungal pathogen Candida albicans is able to drastically change cell morphology to evade mammalian immune responses. The oval yeast form is mostly associated with the commensal (benign) state, whereas the elongated hyphal form is linked to pathogenesis. Host factors also determine disease outcome, as the distinct fungal forms are differentially recognized by the innate immune system. In particular, macrophages are able to induce several inflammatory responses that are thought to protect hosts from fungal infections. However, the role of the different fungal morphologies and innate immunity during pathology are not fully understood at the mechanistic level. We established live cell imaging to monitor C. albicans infection of bone marrow derived macrophages, and used fungal mutants with distinct morphogenesis defects, as well as macrophages derived from mice mutant in immune response pathways, to understand how C. albicans causes macrophage cell death, and how it escapes. We show that C. albicans kills macrophages with a biphasic profile, and that an interplay between host pathways and fungal cell morphology and cell surface architecture controls this process. The transcriptional regulator Mediator is a central factor orchestrating morphogenesis upon phagocytosis of C. albicans by macrophages, as well as modulating hyphal cell surface organisation, with individual subunits playing distinct roles. Our data provides new insight into the complex, but carefully regulated interaction between immune cells and fungal pathogens that ultimately determines infections in hosts.