A novel potentiometric sensor was prepared, characterized and utilized for static and continuous determination of cefazolin sodium (CFZN). Several metal-ion complexes and anion exchangers were tested as electroactive materials in plasticized polymeric membranes for selective detection of CFZN. Among different electroactive species tridodecyl methyl ammonium chloride (TDMAC) doped membrane electrode was found to exhibit optimal response characteristics. The optimized membrane sensor exhibited near-Nernstian responses (-55.64 mV decade-1) over CFZN concentration range of 0.41–10 mM as measured in 50 mM acetate buffer, pH 5.5. The proposed sensor offers the advantage selectivity, does not require pre-treatment and possible interfacing with computerized and automated systems. It is worth noting that the developed membrane electrode exhibited good selectivity toward CFZN over other cephalosporins such as; cefradine, ceftazidime, cefadroxil, cefaclor and cefoperazone, as well as some additives encountered in the pharmaceutical preparations and so these sensors were successfully used for determination of CFZN. A tubular-type detector incorporating a TDMAC based membrane sensor was prepared and used under hydrodynamic mode of operation for continuous CFZN quantification. The tubular-type detector exhibited a concentration range from 0.5-10 mM with a near-Nernstian response (-53.91 mV decade-1). Continuous monitoring of CFZN offers the advantages of simple design, ease of construction and possible applications to small volumes of drug solutions without pre-treatment. The developed sensor was utilized successfully in static and continuous modes of operation for the determination of CFZN in dosage forms. The results obtained were in good agreement with the standard method of CFZN analysis.