As cyanobacterial blooms intensify globally, persistent microcystins (MCs) in surface waters present a growing water-quality challenge. Engineered solutions exist but are often costly and impractical for large-scale or natural settings. In contrast, wetlands, with their diverse microbial assemblages and habitats, offer a promising but underexplored pathway for MC removal. We tested this potential through in situ mesocosm experiments in two prairie wetlands; a hypereutrophic system receiving livestock and urban wastewater, and a less-impacted meso‑eutrophic site. Microcystin degradation was measured using 15N-labelled MC-LR added to mesocosms containing water, sediments, and macrophytes under natural conditions. Toxin concentrations declined in all treatments, with decay rates of 0.05-0.23 d-1, consistent with the lower end of laboratory-reported values. Isotope tracing and congener analysis revealed limited incorporation of MCs into sediments or plant tissues, pointing to planktonic degradation by microbes and possibly photolysis as the dominant pathways. Despite high ambient toxin levels, upscaling experiment results to an entire ecosystem suggested that wetlands degrade or retain 99% of MCs, effectively eliminating export to downstream ecosystems.