Chemical pollution reshapes food web responses to species loss.

Chemical pollution and species loss of large organisms are defining features of aquatic ecosystems in the Anthropocene. Owing to the persistent nature of chemical pollutants and the unpredictability of species loss, an understanding of how aquatic ecosystems respond to these combined stressors is lacked. Here, we exposed freshwater mesocosms harboring a diverse community to chemical mixtures (exemplified by per- and polyfluoroalkyl substances, PFAS), nutrient enrichment, and their combined stress, where species loss was simultaneously simulated by removing predators and large aquatic plants. PFAS drove species replacement in intermediate consumers, triggered plankton reassembly, and suppressed energy flow within food webs. Nutrient enrichment promoted primary producers, strengthened bottom‑up energy flow, and reduced plankton functional redundancy. Pre-existing chemical pollution altered the trophic cascade responses following abrupt species loss. After species loss, PFAS stress history rapidly expanded tolerant taxa and declined sensitive species. Nutrient enrichment history facilitated opportunistic plankton expansion. Both before and after species loss, the combination of PFAS and nutrient enrichment induced cross‑tolerance in the community and rewired trophic linkages. Notably, abrupt species loss declined keystone species, collapsed primary productivity, and altered greenhouse gas emission patterns. These findings deepen the understanding of how chemical stress shapes ecosystem resilience and support coordinated pollution control, ecological restoration, and more resilient freshwater management strategies.