Miniaturized and simplified sample preparation methods with reduced consumption of chemicals and non-halogenated solvents are presented for the determination of 12 sulfonamides in baby foods. Hydrophilic interaction liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was used for the identification and quantification of the compounds based on the acquisition of full spectrum at high resolution with accurate mass for precursor and its fragment ions. Three miniaturized protocols based on QuEChERS, salting-out assisted liquid-liquid extraction or low-temperature cleanup were evaluated regarding the extraction efficiency and removal capability of matrix co-extractives. All approaches achieved satisfactory recoveries (70.0–120.0%); however, the miniaturized QuEChERS distinguished by lower co-extractives content in the final extract providing lower matrix effects. Thus, the performance characteristics of the miniaturized QuEChERS were established using different matrices: beef-, egg yolk- and vegetable-based baby food or chicken- and vegetable-based baby food, in compliance with the Codex Alimentarius Commission guidelines. The target compounds were investigated in 30 commercial baby foods.