A method for the determination of 20 pesticides residues in wheat by QuEChERS coupled with GC-MS/MS was developed. The effect of sorbent for purification was investigated. The matrix effect was also studied. The results showed that: (1) Compared with pretreatment method in 7.1.2 of GB 23200. 113—2018, this method reduced the amount of anhydrous MgSO4 added from 1200 mg to 400 mg, the amount of PSA added from 400 mg to 100 mg, and the amount of C18 added from 400 mg to 200 mg. Also, the add 100 mg GCB that could effectively remove the pigment in the wheat extract by optimizing the purification adsorbent. (2) The calibration curves of the 20 pesticides showed good linearity in the range of 5–500 ng/mL with the correlation coefficients (R2) greater than 0.99. The LOD ranged from 0.01 to 0.16 μg/kg and LOQ ranged from 0.04 to 0.52 μg/kg for 20 pesticides. The matrix effects of the 20 pesticides varied greatly. (3) At the spiked level of 80.0 μg/kg, 200.0 μg/kg and 400.0 μg/kg the average recoveries were 75.24%-98.29%, 82.01%-105.71% and 94.91%-106.14% respectively, and relative standard deviations (RSDs) were 0.57%-3.13%, 0.67%-3.98% and 1.26%-3.08% respectively. The method met the requirements of pesticide residue analysis.