Most hosts are infected with multiple parasites, and responses of the immune system to co-occurring parasites may influence disease spread. Helminth infection can bias the host immune response toward a T-helper type 2 (Th2) over a type 1 (Th1) response, impairing the host’s ability to control concurrent intracellular microparasite infections and potentially modifying disease dynamics. In humans, immune-mediated interactions between helminths and microparasites can alter host susceptibility to diseases such as HIV, tuberculosis (TB), and malaria. However, the extent to which similar processes operate in natural animal populations and influence disease spread remains unknown. We used cross-sectional, experimental, and genetic studies to show that gastrointestinal nematode infection alters immunity to intracellular microparasites in free-ranging African buffalo (Syncerus caffer). Buffalo that were more resistant to nematode infection had weaker Th1 responses, there was significant genotypic variation in nematode resistance, and anthelminthic treatment enhanced Th1 immunity. Using a disease dynamic model parameterized with empirical data, we found that nematode-induced immune suppression can facilitate the invasion of bovine TB in buffalo. In the absence of nematodes, TB failed to invade the system, illustrating the critical role nematodes may play in disease establishment. Our results suggest that helminths, by influencing the likelihood of microparasite invasion, may influence patterns of disease emergence in the wild.