Guazatine is a fungicide used in agriculture to control a wide range of seed-borne diseases of cereals and other vegetable foods. In this work, a LC-ESI-MS method was developed for the quantitative detection of guazatine residues in maize and hard wheat. Quantitative data were determined for the residues of the main diamines, triamines, and tetramines that cover more than 87% of the total contents of the mixture. The mean recoveries from the fortified cereals at 0.050 mg/kg ranged from 81 to 86%, with the coefficients of variation (CVs) ranging from 0.9 to 5.5% (n = 5). At 0.025 mg/kg, the recoveries ranged from 78 to 87%, with the CVs ranging from 0.8 to 6.3% (n = 5). The limits of quantification have been estimated to be 0.010, 0.004, 0.002, 0.002, 0.005, and 0.002 mg/kg, respectively, for GN, GG, GNG, GGN, GGG, and GGGG in maize and hard wheat (S/N ratio >10).