Zygomycosis is a rare but very aggressive fungal infection mainly seen in immunocompromised patients. Immediate diagnosis and treatment with antifungal therapy, control of underlying disease, and early surgical debridement is essential. We present two cases of head zygomycosis treated with systemic liposomal amphotericin B, surgical debridement, and immediate free flap reconstruction. A retrospective chart review of two cases of zygomycosis was performed; one with rhino-sino-orbital-cerebral and the other with scalp/cranial zygomycosis. Both patients were treated with systemic liposomal amphotericin B, aggressive debridement, and immediate reconstruction following local control. The multidisciplinary team approach and the surgical technique are discussed. Patient 1 (with rhino-sino-orbital-cerebral zygomycosis) died 2 weeks after diagnosis, and patient 2 (with scalp/cranial zygomycosis) was disease free at 1-year follow-up. Both patients' flaps survived, although patient 2 needed to undergo an arterial revision with an interpositional vein graft within 24 hours of surgery. We concluded that to treat zygomycosis effectively, a multidisciplinary team approach is needed, focusing on immediate diagnosis, empirical antifungal therapy, reversal of underlying predisposing factors, and early surgical debridement. When definitive debridement results in critical structures being exposed, then early wound closure with healthy vascularized tissue is indicated. In these two patients with exposed dura after definitive debridement, immediate closure was performed to minimize the risk of meningeal and cerebral infections.