A simple, rapid, sensitive, accurate and reliable multiresidue method based on ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) is developed and validated for the simultaneous determination of 13 quinolone derivatives in urban wastewaters. The main parameters influencing the preliminary sample treatment and selective solid‐phase extraction procedure have been analyzed in order to optimize a suitable procedure for extraction of amphoteric and acidic quinolones in one single step. Matrix components of wastewater samples were significantly reduced and even eliminated. The mass spectrometric conditions in positive electrospray ionization (ESI) mode were individually optimized for each analyte to obtain maximum sensitivity in the Selected Reaction Monitoring (SRM) mode. Selection of two specific fragmentation reactions for each compound allowed simultaneous quantification and identification in one run, ensuring a high specificity of the method. The analytes were separated in less than 10min. Marbofloxacin and cincophen were used as surrogates for amphoteric and acid quinolones, respectively. The limits of detection ranged from 0.02 to 0.04ngmL −1 and limits of quantification from 0.07 to 0.15ngmL −1 , while inter‐ and intra‐day variabilities were <4%. Due to the absence of certified materials, the method was validated using matrix‐matched calibration and a recovery assay with spiked samples. Recovery rates ranged from 98.5% to 103.9%. The method was satisfactorily applied for the determination of these antibiotics in wastewater samples collected from different wastewater treatments plants from the province of Granada (Spain). In addition, the method will be applied in further studies of the occurrence and fate of these commonly used antibiotics in sewage treatment plants and in aquatic environments.