There are increasing concerns about the danger that water-borne pathogens and pollutants pose to the public. Of particular importance are those that disrupt the plasma membrane, since loss of membrane integrity can lead to cell death. Currently, quantitative assays to detect membrane-disrupting (lytic) agents are done offsite, leading to long turnaround times and high costs, while existing colorimetric point-of-need solutions often sacrifice sensitivity. Thus, portable and highly sensitive solutions are needed to detect lytic agents for health and environmental monitoring. Here, a lipid-based electrochemical sensing platform is introduced to rapidly detect membrane-disrupting agents. The platform combines benchtop fabricated microstructured electrodes (MSEs) with lipid membranes. The sensing mechanism of the lipid-based platform relies on stacked lipid membranes serving as passivating layers that when disrupted generate electrochemical signals proportional to the membrane damage. The MSE topography, membrane casting and annealing conditions were optimized to yield the most reproducible and sensitive devices. We used the sensors to detect membrane-disrupting agents sodium dodecyl sulfate and Polymyxin-B within minutes and with limits of detection in the ppm regime. This study introduces a platform with potential for the integration of complex membranes on MSEs towards the goal of developing Membrane-on-Chip sensing devices.