The oriental fruit fly, Bactrocera dorsalis (Hendel), is a globally important economic insect pest that has evolved resistance to various types of insecticides. Cyantraniliprole (DuPont Cyazypyr) is a new anthranilic diamide insecticide registered to control lepidopteran and sucking insects. The susceptibility of field-collected populations of B. dorsalis to cyantraniliprole was assessed via a diet incorporation bioassay in adults. Based on the obtained LC₅₀ values (ranging from 3.29 to 15.83 µg/g), all the testing populations, including ZZ (Fujian province), HH (Yunnan province), JM (Guangdong province), SY (Hainan province), HZ (Zhejiang province), YL (Guangxi province), SH (Shanghai), WH (Hubei province), and CS (Hunan province), were susceptible to cyantraniliprole, with the samples of WH (Hubei province) being the most tolerant (by 4.80-fold). Two (SY, Hainan province; CS, Hunan province) of the nine field-collected populations of B. dorsalis showed a similar susceptibility to cyantraniliprole, while the remaining populations displayed narrow variations in tolerance compared with the laboratory strain. Synergist assays were performed to determine the potential detoxification mechanisms. Piperonyl butoxide showed significant synergism effects in lab, CS, and resistant strain. S,S,S-tributylphorotrithioate and diethyl maleate also showed obvious synergism effects in resistant strain. A 19.44-fold increase in resistance to cyantraniliprole was observed after 14 generations of selection in the laboratory. The present work clarifies the baseline susceptibility and primary mechanisms of B. dorsalis to cyantraniliprole in the south China and established a cyantraniliprole-resistant strain as well. A sound resistance management strategy is also discussed in relation to the risk of susceptibility.