plays a vital role in biological metabolisms, for example, the digestion of amino acids, as well as the synthesis of adrenalin, certain hormones, and neurotransmitters. [2] AA has also been commonly used for the prevention and treatment of scurvy, [3] cancer, [4] common cold, [5] and AIDS, [6] etc. The design and implementation of cost-effective, high-performance electrochemical sensors for the rapid and accurate quantification of AA concentration in foods or biological fluids are important for many societally pervasive applications such as clinical diagnostics, [7] wearable health monitoring, [8] food safety, [9] and environmental monitoring. [10] However, the direct electrooxidation of AA on the surface of the bare electrodes is irreversible. [11] Moreover, the subsequent hydrolysis of the reaction will cause electrode fouling with large overpotential, poor selectivity, low sensitivity, and unsatisfactory reproducibility. [12] Nanostructured catalysts with large specific surfaces and abundant active sites appeal to highly sensitive electrochemical sensing of various chemicals. Various nanomaterials, such as conducting polymers, [13] carbon materials, [14] and metal oxides, [15] have been explored for modifying the electrodes to efficiently detect AA, Nanostructured piezoelectric semiconductors offer unprecedented opportunities for high-performance sensing in numerous catalytic processes of biomedical, pharmaceutical, and agricultural interests, leveraging piezocatalysis that enhances the catalytic efficiency with the strain-induced piezoelectric field. Here, a cost-efficient, high-performance piezo-electrocatalytic sensor for detecting l-ascorbic acid (AA), a critical chemical for many organisms, metabolic processes, and medical treatments, is designed and demonstrated. Zinc oxide (ZnO) nanorods and nanosheets are prepared to characterize and compare their efficacy for the piezo-electrocatalysis of AA. The electrocatalytic efficacy of AA is significantly boosted by the piezoelectric polarization induced in the nanostructured semiconducting ZnO catalysts. The charge transfer between the strained ZnO nanostructures and AA is elucidated to reveal the mechanism for the related piezo-electrocatalytic process. The lowtemperature synthesis of high-quality ZnO nanostructures allows low-cost, scalable production, and integration directly into wearable electrocatalytic sensors whose performance can be boosted by otherwise wasted mechanical energy from the working environment, for example, human-generated mechanical signals.