The oriental fruit fly, Bactrocera dorsalis (Hendel), is a serious insect pest that causes large losses to orchards globally. In this study, we conducted experiments to investigate the susceptibility of two populations (Kunming of Yunnan and Dongguan of Guangdong province) of B. dorsalis to nine insecticides. Bioassay results demonstrated that fipronil was the most effective insecticide, followed by phoxim, abamectin, triazophos, β-cypermethrin, chlorpyrifos, deltamethrin, malathion, and imidacloprid against the Kunming of Yunnan province population, with LD₅₀ values that ranged from 1.55 to 187.48 ng/ fly. For the Dongguan of Guangdong province population, fipronil was also most toxic, followed by triazophos, phoxim, chlorpyrifos, abamectin, deltamethrin, β-cypermethrin, malathion, and imidacloprid, with LD₅₀ values from 2.07 to 439.11 ng/fly. The addition of synergists triphenyl phosphate, piperonyl butoxide, and diethyl maleate yielded different levels of synergistic effects on different insecticides against each population. However, the synergistic effects on the nine insecticides against the two populations are different. The treatment of a sublethal dose (LD₂₀) of λ-cypermethrin together with three synergists could induce increased specific activity of carboxylesterases at the beginning of exposure, followed by a decline within 24 h. The specific activity of carboxylesterases was higher in the fat body, midgut, and Malpighian tubules, suggesting these are important tissues for detoxification. Overall, the data developed in this study provide useful information for designing an insecticide management strategy for controlling this insect in the field.