Wastewater treatment plants receiving a combination of municipal and industrial flows face increasing operational complexity due to variable organic loading, wet-weather inflow and infiltration, and tightening performance expectations. Oxidation ditch facilities are particularly sensitive to these disturbances, where delayed detection of influent upsets can result in biomass stress, energy inefficiency, or compliance risk. This case study presents the application of real-time biological response monitoring at the Frankfort Wastewater Treatment Plant (Kentucky, USA), demonstrating how continuous monitoring of consumable organic loading can support operator decision-making and operational innovation. The Frankfort facility serves approximately 30,000 people and treats wastewater from more than a dozen industrial contributors, including upstream distilleries. The treatment process consists of three parallel oxidation ditches that are hydraulically and operationally distinct. Historically, the plant experienced episodic biological stress events linked to industrial discharges and wet-weather conditions, with limited ability to distinguish between true organic loading events, dilution, and normal operational variability using conventional grab sampling and laboratory analyses. Bio-electrochemical sensors were deployed to continuously monitor influent conditions and downstream biological response across the oxidation ditches. The monitoring system measures a real-time biological activity signal generated by anaerobic electroactive bacteria embedded in the sensor. These organisms produce a small electrical current as they metabolize readily biodegradable organic compounds, and the measured signal reflects the rate at which carbon is being biologically consumed rather than the concentration of organic matter. As a result, the signal responds rapidly to changes in available bacterial “food” as well as to compounds that inhibit microbial metabolism, providing immediate insight into both loading and toxicity effects. Over more than one year of operation, high-resolution data were translated into monthly, operator-focused reports highlighting key events, performance indicators, and ditch-specific behavior. The data revealed consistent, repeatable biological “fingerprints” for each oxidation ditch, clearly distinguishing differences in buffering capacity, sensitivity to rainfall, and response to operational controls such as aeration and flow routing. Real-time monitoring enabled early detection of high organic loading events, identification of rainfall-driven dilution and first-flush effects, and visualization of how influent disturbances propagated through the biological process with measurable time delays. Importantly, operators were able to separate operation-driven variability from external disturbances, improving confidence in process adjustments during wet-weather events and periods of atypical industrial loading. In several instances, the same rainfall event produced opposite biological responses across parallel ditches, highlighting the value of ditch-specific insight rather than plant-wide assumptions. Beyond event detection, the continuous biological response signal provided a foundation for operational innovation. By linking incoming organic load to biological demand in near real time, the monitoring approach supported informed aeration decision-making and identified opportunities for load-based aeration control and energy optimization. This case study illustrates how real-time biological response monitoring can function as a practical decision-support tool, enhancing resilience, situational awareness, and proactive control in oxidation ditch wastewater treatment systems.