Ascorbic Acid (AA) has been the center of controversial dialogues and studies when it comes to cancer research, though recently it has gained interest as an anti-tumor agent. Here, we present an electroanalytical concept to determine AA based on a new fundamental finding: the reversible interaction of AA with carbon nanotubes (CNTs) under zero-current measurements (potentiometry). This interaction is systemically studied under several experimental conditions, aiming to provide specificity with the combination of a thin film of CNTs with a nanometer-sized plasticized polymeric membrane (ca. 300 nm in thickness). The resulting sensor shows a consistent sensitivity to AA of –33.53 ± 2.57 mV/decade (n = 17), presenting a linear range of response that includes from normal physiological to pharmacological AA concentrations (10–200 μM and 0.2–1 mM, respectively). Importantly, interferences such as uric acid (UA), sodium ion and lactate have a limited influence on the potentiometric response, in contrast to previously published sensors. In addition to the experimental evidence, computational simulations on the interactions of AA and UA with a graphene-based model were performed to provide insights in describing the very distinct experimental responses that were observed. Thus, the formulated hypothesis is supported by both experimental data and simulations, which has not been reported before, to the best of our knowledge. Furthermore, we demonstrate the suitability of the developed sensor for real sample analysis (undiluted human serum, saliva and urine). The significance of the developed sensor is three-fold: 1) analytical performance addressing several applications, 2) enhanced selectivity, specially towards UA, 3) simplicity of the concept in terms of materials and preparation that makes it compatible with micro- and nano-electrodes for further analytical applications never explored until now (e.g., intracellular measurements, nanoelectrochemistry, etc.)