Sulfonamides, the most frequent antibacterial agent, are widely used due to their low cost and excellent antibacterial effect. With the emergence of the environment, the potential hazard to the ecological environment has attracted the great attention of humans. Based on matrix solid‐phase dispersion coupled with high‐performance liquid chromatography‐tandem mass spectrometry, an accurate, fast, and sensitive analytical method was developed for the determination of sulfonamides (SAs) in soil. Several influencing factors including the type of dispersants, the ratio of sample‐to‐sorbent, eluents, and solvent volume were investigated, and the matrix effects were evaluated. Under optimized conditions, the calibration curves exhibited excellent linearity with correlation coefficients (r) exceeding 0.996. The limit of detection (based on signal‐to‐noise ratio [S/N] = 3) and limit of quantification (based on S/N = 10) were 0.024–0.058 and 0.079–0.195 µg/kg, respectively. The recoveries ranging from 70.12% to 123.63% were obtained with a relative standard deviation of less than 15% at three levels (20, 40, and 200 µg/kg). The developed method was successfully applied to analyze 13 SAs at trace levels in a real soil sample. This proposed method would be an alternative and suitable for routine application in the future owing to its rapidity, sensitivity, and affordability.