The effects of configurational changes among nine plasticizers were studied using puncture tests. Ion-selective poly(vinyl chloride) (PVC) membranes were plasticized with three citrate-related compounds (Citroflex A-4 (CFA4), Citroflex A-6 (CFA6), and Citroflex B-6 (CFB6)) and six sebacate-related compounds (dimethyl sebacate (DMS), diethyl sebacate (DES), dibutyl sebacate (DBS), dioctyl sebacate (DOS), dioctyl azelate (DOZ), and dioctyl adipate (DOA)). The strengths, stiffnesses, and toughnesses of the membranes increased at low PHR ratios (which are defined as the actual concentrations of plasticizer to PVC divided by the minimum concentrations of plasticizer required to isolate all of the PVC polar groups) and then monotonically decreased as plasticizer was added above these ratios. The ductilities increased up to PHR ratios of about 2.0 and decreased above PHR ratios of about 4.0. The citrate-related compounds could not be distinguished according to the mechanical properties. The DMS-, DES-, and DOA-plasticized membranes were generally stronger and stiffer than the DBS-, DOS-, and DOZ-plasticized membranes, but the ductilities were reduced using DMS, DES, and DOA. A nomogram was constructed to predict the strength, based on the plasticizer selection and PHR ratio. The strengths, stiffnesses, and toughnesses of the membranes decreased as the log (ionic conductivity, sigma) increased, and the ranking of the configurational differences was similar to those of the mechanical properties versus PHR ratio.