This study aims to establish a rapid, accurate, safe, inexpensive, and effective method that combines QuEChERS pre-treatment with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 20 benzodiazepine sedatives (SDTs) and 4 eugenol anaesthetics (AETs) in chicken, canned fish, meat floss, and powdered milk such that technical support can be provided for monitoring residues of 24 SDTs and AETs in the food matrix and for protecting human life and health. Results demonstrated that all 24 SDTs and AETs exhibited good linearity in their corresponding concentration ranges with correlation coefficients (r) of > 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were in the ranges of 0.01–0.22 and 0.03–0.67 µg∙kg−1, respectively, and the recoveries were in the range of 70.04–110.26% (n = 7) with precision in the range of 0.75–9.99% (n = 7) for 24 SDTs and AETs at different concentrations (4, 20, and 100 µg∙kg−1). This method was successfully applied to real samples and provides a convenient tool for detecting residues of SDTs and AETs in animal-derived foods.