A wide range of mammals are susceptible to infection by the fungal species Coccidioides immitis and C. posadasii. In humans, 60% of infections are asymptomatic; however, certain patients may develop a severe and deep systemic mycosis called coccidioidomycosis. Genetic analysis suggests that the majority of clinical isolates recovered from South America are C. posadasii; however, little is known about the prevalence, species distribution, and ecological factors that favor the occurrence of this pathogen in those areas. By using a combined quantitative polymerase chain reaction (qPCR)-based approach and mycobiome amplicon sequencing, we provide evidence that at least two genotypes of C. posadasii are found in the xerophytic environment in Venezuela. We detected a 3806-fold range in the amount of Coccidioides DNA when comparing among the sampled locations, which indicates that human exposure risk is variable, and is one critical factor for disease manifestation. We identified fungal communities that are correlated with a higher prevalence of C. posadasii, suggesting that a combination of specific microbes and a xeric microenvironment may favor the growth of Coccidioides in certain locations. Moreover, we discuss the use of a combinatorial approach, using both qPCR and deep-sequencing methods to assess and monitor fungal pathogen burden at outbreak sources.