Bioelectrochemistry employs an array of high-surface area meso and macroporous electrode architectures to increase protein loading and the electrochemical current response. Whilst the local chemical environment has been studied in small molecule and heterogenous electrocatalysis, conditions in enzyme electrochemistry are still commonly established based on bulk solution assays, without appropriate consideration of the non-equilibrium conditions of the confined electrode space. Here, we apply electrochemical and computational techniques to explore the local environment of fuel-producing oxidoreductases within porous electrode architectures. This improved understanding of the local environment enabled simple manipulation of the electrolyte solution, by adjusting the bulk pH and buffer pKa, to achieve an optimum local pH for maximal activity of the immobilised enzyme. When applied to macroporous inverse opal electrodes, the benefits of higher loading and increased mass transport were employed and, consequently, the electrolyte adjusted to reach −8.0 mA cm −2 for the H2 evolution reaction (HER) and −3.6 mA cm −2 for the CO2 reduction reaction (CO2RR), demonstrating an 18-fold improvement on previously reported enzymatic CO2RR systems. This research emphasises the critical importance of understanding the confined enzymatic chemical environment, thus expanding the known capabilities of enzyme bioelectrocatalysis. These considerations and insights can be directly applied to both bio(photo)electrochemical fuel and chemical synthesis as well as enzymatic fuel cells to significantly improve the fundamental understanding of the enzyme-electrode interface as well as device performance.