Hydrophobic gating in biological transport proteins is regulated by stimulus-specific switching between filled and empty nanocavities, endowing them with selective mass transport capabilities. Inspired by these, solid-state nanochannels have been integrated into functional materials for a broad range of applications, such as energy conversion, filtration, and nanoelectronics, and here we extend these to electrochemical biosensors coupled to mass transport control elements. Specifically, we report hierarchically organized structures with block copolymers on tyrosinase-modified two-electrode nanopore electrode arrays (BCP@NEAs) as stimulus-controlled electrochemical biosensors for alkylphenols. A polystyrene-<i>b</i>-poly(4-vinyl)pyridine (PS-<i>b</i>-P4VP) membrane placed atop the NEA endows the system with potential-responsive gating properties, where water transport is spatially and temporarily gated through hydrophobic P4VP nanochannels by the application of appropriate potentials. The reversibility of hydrophobic voltage-gating makes it possible to capture and confine analyte species in the attoliter-volume vestibule of cylindrical nanopore electrodes, enabling redox cycling and yielding enhanced currents with amplification factors >100× when operated in a generator-collector mode. The enzyme-coupled sensing capabilities are demonstrated using nonelectroactive 4-ethyl phenol, exploiting the tyrosinase-catalyzed turnover into reversibly redox-active quinones, then using the quinone-catechol redox reaction to achieve ultrasensitive cycling currents in confined BCP@NEA sensors giving a limit-of-detection of ∼120 nM. The mass transport controlled sensing platform described here is relevant to the development of enzyme-coupled multiplex biosensors for sensitive and selective detection of biomarkers and metabolites in next-generation point-of-care devices.