Insect tolerance to insecticides is closely related to the host plant. Migratory insects flying downwind and landing randomly may face host-plant switching after migration. However, it is not clear whether host-plant switching affects the tolerance of migratory insects to insecticides. In the present work, Cnaphalocrocis medinalis, a migratory pest destructive to rice, was studied to explore this issue. The results show that the host-plant switch reduced the susceptibility of rice and wheat larvae populations to abamectin but increased that of wheat larvae populations to chlorpyrifos, indicating that host switching resulted in different tolerance to different insecticides. Enzyme activity determination showed that, although abamectin and chlorpyrifos affect the activities of detoxification enzymes (carboxylesterase, multifunctional oxidase, and glutathione S-transferases), antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), and acetylcholinesterase at sublethal dosages, the effect depends on the host plant and insecticide species. Overall, our findings show that the induction of C. medinalis by host switching affects its susceptibility and biochemical responses to abamectin and chlorpyrifos. Insecticides against C. medinalis should be used with consideration of the potential impact of host switching. Reasonable selection and usages of insecticides can help in the resistance management and control of migratory insects.