In 2004, the Food Code of Korea adopted a multi-class multi-residue pesticide analysis method, which employed liquid–liquid extraction (LLE) and solid-phase extraction for sample purification. After several modifications, the LLE stage was replaced by the QuEChERS method in October 2021. Thus, in the current study a comparison was carried out between the new QuEChERS method and the conventional LLE method for the simultaneous analysis of multiple pesticide residues. More specifically, 275 pesticide compounds were measured in spinach, rice, and mandarin matrices using LC-MS/MS, and the linearity, LOD, LOQ, recovery, and matrix effect were determined. Following both the QuEChERS and LLE, the matrix-matched calibration curve plotted using the extracts of blank matrix extracts showed that the majority of pesticides exhibited a highly linear relationship, with coefficients of determination >0.99. In addition, the LOD was 0.00003–0.004 mg/kg, and the LOQ was 0.0001–0.01 mg/kg. For the different matrices, the average recovery of the QuEChERS method was 101.3–105.8%, while that of the LLE method was 62.6–85.5%. Due to the fact that the LLE and QuEChERS methods exhibited a tendency of suppression for the various matrices examined, matrix-matched calibration was required during quantification. Indeed, introduction of the QuEChERS method allowed matrix-matched calibration to be conducted during quantification, while the previously employed LLE method did not involve such processes. These changes therefore resulted in a more accurate quantification in addition to a reduced experimental time and cost. • We compared QuEChERS to LLE in multi-residue analysis in foods by LC-MS/MS. • QuEChERS has higher and more uniform recovery rates among matrices than LLE. • Both methods require matrix-matched calibration owing to ion suppression. • QuEChERS and matrix-matched calibration improve quantification accuracy.