A simple, reliable, and rapid HPLC analysis is proposed for the quantification of ten cephalosporins; Cefepime, Ceftazidime, Cefuroxime, Cefaclor, Ceftriaxone, Cefazolin, Cefadroxil, Cefotaxime, Cephalexin and Cephapirin, simultaneously, in wastewater from factories as a tool at the local level for regular environmental monitoring program. The water samples are directly used, with no complicated sample pretreatment steps. The separation was accomplished on C18 reversed-stationary phase and the mobile phases were composed of methanol:0.1% pentane sulfonic acid (22:78) at pH 2.5 with 1.2 mL/min flow rate (system 1) and methanol:phosphate buffer (27:73, pH 7) with 1.0 mL/min flow rate (system 2). 265 and 235 nm are the optimum wavelengths used for UV detection for system 1 and system 2, respectively. Under the optimized conditions, very low LODs and LOQs were obtained for all the studied compounds. The quantification of various cephalosporins in real water was accomplished. Both the effluent and influent of the local wastewater showed negative results, indicating that the obtained waste water is free from cephalosporin antibiotics.