In this study, a simple, inexpensive and sensitive method named emulsification liquid–liquid microextraction based on deep eutectic solvents (ELLME-DES) was used for the extraction of sulfonamides (SAs) from water samples, including sulfadiazine (SDZ), sulfamerazine (SMR), sulfametoxydiazine (SDD) and sulfamethoxazole (SMX). In a typical experiment, eight kinds of DESs (as water-miscible extraction solvents) were added to 1.5 mL of sample solution containing target analytes, respectively. A homogeneous solution was formed immediately. Injection of THF (as an emulsifying agent) into the homogeneous solution provided a turbid state. After extraction, phase separation (aqueous phase/DES rich phase) was performed by centrifugation. The DES rich phase was withdrawn using a micro-syringe and submitted to isocratic reverse-phase HPLC with UV detection. Under optimum conditions obtained by response surface methodology (RSM) and the desirability function, the best conditions were when the parameters were 193 μL of DES4, 100 μL of THF and an ultrasonication time of 17 min. The recoveries of SDZ, SMR, SDD and SMX were 86.54%, 88.48%, 80.78% and 74.65%, respectively. This procedure was successfully applied to the determination of target analytes in spiked water samples. It showed highly satisfactory results and potential for rapid extraction of SAs from water samples combining with the method of ELLME-DES.