Among pharmaceuticals, the occurrence of antibiotics in the environment is a subject of special concern due to their environmental impact, namely the development of bacterial resistance. Sulfamethoxazole (SMX) is one of the most commonly used antibiotics and it is regularly found, not only in effluents from sewage treatment plants (STPs), but also in the aquatic environment. Photodegradation appears as an alternative process for the removal of this type of pollutants from contaminated waters. In order to be used for a remediation purpose, its evaluation under continuous flow mode is essential, as well as the determination of the final effluent antibacterial activity, which were assessed in this work. As compared with batch operation, the irradiation time needed for SMX elimination under continuous flow mode sharply decreased, which is very advantageous for the target application. Moreover, the interrelation between SMX removal, mineralization and antibacterial activity was evaluated before and during photodegradation in ultrapure water. Although mineralization was slower than SMX removal, bacterial activity increased after SMX photodegradation. Such increase was also verified in environmental water matrices. Thus, this study has proven that photodegradation is an efficient and sustainable process for both (i) the remediation of waters contaminated with antibiotics, and (ii) the minimization of the bacterial resistance.