Cefotaxime was selectively determined using a sensor based on polymeric membrane electrode. The membrane incorporated a low-cost and commercially available anion exchanger namely tridodecyl methyl ammonium bromide (TDMAB), embedded in a plasticized PVC matrix. The influence of the composition of the membrane (e.g., type and amount of ion exchanger, besides the plasticizer type) on potentiometric behavior of the synthesized membrane electrode was investigated. The optimized membrane electrode showed near-Nernstian response towards cefotaxime with slope of −53.65 mV decade−1. The linear concentration range for the quantitation of cefotaxime sodium was 0.17 – 10 mM. The calculated detection limit was 0.12 mM. The prepared TDMAB based membrane was incorporated in a tubular-type sensor. The sensor was adopted for continuous cefotaxime determination under hydrodynamic mode. The tubular-type sensor showed a near-Nernstian response (−52.90 mV decade−1) in a range of concentrations of 0.5 – 10 mM. The selectivity studies demonstrated that the optimized membrane electrode displayed high selectivity for cefotaxime over several members of anions and other cephalosporin drugs such as; cefaclor, cefadroxil, cefoperazone, cefradine and ceftazidime. The analytical utility of suggested membrane sensor was demonstrated by cefotaxime quantification in different pharmaceutical formulations using both the direct potentiometric and flow-injection methods. The calculated results were in accordance to those obtained using the reported UV–visible method in respect to precision and accuracy.