This study applied comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF-MS) for the analysis of 100 pesticides (77 organophosphorus and 23 organochlorines) in six typical plant matrices with high protein, starch, acid, or oil content. Different sorbents were evaluated in the clean-up step of the QuEChERS method, and the optimized sorbent combinations were obtained for each individual matrix. Good linearity of the calibration curves of matrix-matched was obtained (R2 ≥ 0.9853). The mean recoveries and relative standard deviations at fortification levels of 10 and 50 μg/kg ranged from 72.6 to 117.5% and 0.1 to 19.9%, respectively. Phenolic antioxidants, glycosides, phosphorus esters, linoleic acid, unsaturated fatty acids, and other interferences in individual plant matrix were identified. The results demonstrated that GC×GC-TOF-MS is helpful in separation of the co-eluted pesticides and the identification of interferences in complex plant matrices.