Some of the world’s most devastating phytopathogens display a hemibiotrophic lifestyle consisting of an initial biotrophic phase followed by a late necrotrophic stage characterized by the necrosis of plant tissues. To date, little is known about the molecular mechanisms that promote these distinct phases or those that mediate the transition between them. The causal agent of witches’ broom disease of cacao (WBD), Moniliophthora perniciosa, is a hemibiotrophic basidiomycete with an unusually extended biotrophic (infective) stage that causes remarkable morphophisiological alterations in cacao plants. The initial biotrophic mycelium is monokaryotic and morphologically distinct from the subsequent dikaryotic necrotrophic mycelium. Here, we report the characterization of an alternative oxidase gene (Mp-aox) identified in the M. perniciosa genome, whose expression was closely associated with the fungal hemibiotrophic lifestyle. A large number of Mp-aox transcripts was observed in the monokaryotic hyphae, which also showed an elevated sensitivity to AOX inhibitors. More importantly, inhibition of the cytochrome-dependent respiratory chain (CRC) prevented the transition from the monokaryotic to the dikaryotic phase, and the combined use of a CRC inhibitor with an AOX inhibitor completely halted M. perniciosa growth. Based on these results, we present a model in which the functionality of the mitochondrial respiratory pathways plays a central role in the hemibiotrophic development and pathogenicity of M. perniciosa. Strikingly, our model correlates well with the infection strategy described for animal pathogens, particularly Trypanosoma brucei, which uses the alternative respiratory route as a strategy for pathogenicity.