Sulfadiazine (SD) and sulfamethoxazole (SMX) are widely used sulfonamide antibiotics, which are present as contaminants in surface waters and are known to undergo phototransformation. This kinetic study was conducted to identify the processes responsible for their phototransformation in sunlit surface waters. Water samples from the Thur River (Switzerland) and from a pilot wastewater treatment plant, as well as aqueous solutions of two well-characterized natural dissolved organic matter (DOM) extracts, namely Suwannee River and Pony Lake fulvic acids (SRFA, PLFA), were examined. Both sulfonamides were found to undergo direct and indirect phototransformation, with contributions of excited triplet states of DOM and of effluent organic matter (EfOM) and possibly of hydroxyl radical and other unidentified reactive species. Under simulated sunlight, SMX mainly reacted through direct phototransformation, with a certain contribution of indirect phototransformation occurring for a wastewater effluent. The behavior of SD was found to be more diverse. For river waters, wastewater effluents and PLFA solutions, indirect phototransformation was predominant, while for SRFA solutions direct phototransformation prevailed. The rates of phototransformation of SD were interpreted as the result of a complex interplay between the photosensitizing and the inhibitory effect of DOM/EfOM, with an additional component related to the nitrite ion as a source of photoproduced hydroxyl radical. For typical conditions found in surface waters comparable to the Thur River, phototransformation half-lives on the order of 3–13 d were estimated for the two studied sulfonamides.