Incorporation of introduced plant species into the diets of native insect herbivores is a common phenomenon; however, herbivore performance is often reduced on these exotic plants. Investigating the impacts of exotic plant use on herbivore interactions with pathogens may provide insight into the costs and benefits of dietary expansion. Here, we evaluated the hypothesis that improved defense against disease may facilitate herbivore persistence on introduced plants that confer relatively poor performance. Utilizing a combination of field surveys and manipulative experiments, we examined how use of a recently incorporated plant, Plantago lanceolata, impacted immunity, chemical defense, and interactions with a virus in two North American butterflies: Euphydryas phaeton and Anartia jatrophae. The focal pathogen, Junonia coenia densovirus, was found to be widespread in E. phaeton and A. jatrophae populations, and viral sequencing revealed low levels of genetic divergence across host species and populations. E. phaeton caterpillars using the exotic plant exhibited reduced immune performance and compositional differences in iridoid glycoside (IG) sequestration. Notably, caterpillars that sequestered higher concentrations of IGs exhibited reduced immunocompetence, but also reduced viral burdens, compared to those with lower sequestration levels. In a related experiment, A. jatrophae caterpillars infected with JcDV experienced lower viral burdens and higher survival when feeding on P. lanceolata, compared to a native plant containing no IGs. These findings illustrate that both physiological defenses and disease outcomes can differ markedly between herbivores utilizing different plant species, highlighting the importance of considering interactions with pathogens within investigations of diet breadth evolution.