The pressures of global change acting on wild plants and animals include exposure to environmental toxins, the introduction of non-native species, and climate change. Relatively few studies have been reported in which these three main classes of stressors have been examined simultaneously, allowing for the possibility of synergistic effects in an experimental context. In this study, we exposed caterpillars of the Melissa blue butterfly (
Lycaeides melissa
) to three concentrations of chlorantraniliprole, under three experimental climates, on a diet of a native or a non-native host plant throughout larval development in a fully factorial experiment. We find that high pesticide exposure and a non-native diet exhibit strong negative effects on caterpillars, resulting in 62% and 42% reduction in survival, respectively, while interactive effects tend to be weaker, ranging from 15% to 22% reduction in survival. Interactive effects have been shown to be strong in other contexts, but do not appear to be universal; however, our study shows that the cumulative effects of stressors acting in isolation (additively) are sufficiently strong to severely reduce survival and by extension population persistence in the wild.