Sulfamethoxazole and trimethoprim are synthetic bacteriostatic drugs. A potentiometric multisensory system for the analysis of sulfamethoxazole and trimethoprim combination drugs was developed. Perfluorosulfonic acid membranes containing functionalized CNTs were used as the sensor materials. The CNTs’ surface was modified by carboxyl, sulfonic acid, or (3-aminopropyl)trimethoxysilanol groups. The influence of the CNT concentration and the properties of their surface, as well as preliminary ultrasonic treatment of the polymer and CNT solution before the casting of hybrid membranes, on their ion-exchange capacity, water uptake, and transport properties was revealed. Cross-sensitivity of the sensors to the analytes was achieved due to ion exchange and hydrophobic interactions with hybrid membranes. An array of cross-sensitive sensors based on the membranes containing 1.0 wt% of CNTs with sulfonic acid or (3-aminopropyl)trimethoxysilanol groups enabled us to provide the simultaneous determination of sulfamethoxazole and trimethoprim in aqueous solutions with a concentration ranging from 1.0 × 10−5 to 1.0 × 10−3 M (pH 4.53–8.31). The detection limits of sulfamethoxazole and trimethoprim were 3.5 × 10−7 and 1.3 × 10−7 М. The relative errors of sulfamethoxazole and trimethoprim determination in the combination drug as compared with the content declared by the manufacturer were 4% (at 6% RSD) and 5% (at 7% RSD).