A rapid and sensitive method for simultaneous quantitative determination of terpenoids in Tripterygium wilfordii Hook F (TwHF) was developed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). In this method, five major terpenoids, including triptolide, triptonide, demethylzelastral, tripterine and wilforlide A, with large content range in TwHF, were determined simultaneously in a UHPLC run of 4.5 minutes. The intra-day and inter-day precisions of five terpenoids were less than 4.58% and 4.82%, respectively, and the mean recovery rates obtained were in the range of 97.2% to 104.5%. All calibration curves showed good linearity (r² > 0.996) from 20 ng mL⁻¹ and 20 000 ng mL⁻¹. The limit of detection (LOD) and limit of quantitation (LOQ) were less than 5.7 ng mL⁻¹ and 19.0 ng mL⁻¹. Compared with previous studies, this method could be employed for accurate quantification of five terpenoids in different parts and products of TwHF in a very short time after simple ultrasonic extraction. The results indicated that this method would provide a rapid and sensitive way for evaluating the quality of the TwHF and its products.