Simazine is widely used to manage weed growth in the agricultural and industrial fields. Three analytical methods, including gas chromatography (GC)/ion-trap (IT), GC/mass selective detector (MSD), and high-performance liquid chromatography (HPLC)/triple quadrupole mass spectrometers (HPLC/MS/MS), were developed and compared for simazine quantification. The spike recoveries by GC/IT, GC/MSD, and HPLC/MS/MS were 100, 117, and 82.5%, respectively. Different spike recovery depending on analytical methods could be due to matrix effect, different instrumental sensitivity, losses during sample preparation or all of the above. The limit of detection was 0.0361, 0.0263, and 0.0013 mg/kg by GC/IT, GC/MSD, and HPLC/MS/MS, respectively. The HPLC/MS/MS with a positive atmospheric pressure chemical ionization (APCI) ionization mode was the most rapid (7 min), sensitive (limit of detection: 0.0013 mg/kg, limit of quantification: 0.0042 mg/kg), and precise (relative standard deviation: 0.5%) method for simazine quantification.