Climate change and anthropogenic activities are expected to impact the environmental behaviors and fates of persistent organic pollutants (POPs), however, quantitative studies on these combined factors are scarce. In this study, dichlorodiphenyltrichloroethane (DDTs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were used as examples to identify how and when those factors may be related to the deposition of POPs in the sediment of Lake Chaohu, China, using generalized additive models (GAMs). Three historical trends of DDT, PAH, and PCB deposition were delineated in a dated sediment core encompassing ~100 years of historical record: a steady state or gradually increasing stage, a rapidly increasing stage, and a declining stage. The GAM results showed that aquatic total phosphorus (TP) concentrations and regional GDP (anthropogenic factors) were dominant contributors to POP accumulation rates in the lake sediment. The fitted relationships between air temperature and sedimentary DDT and PAH concentrations were linear and negative, while a positive linear relationship was found for PCBs, suggesting that Lake Chaohu may have become a net source for DDTs and PAHs, and a sink for PCBs, under a progressively warming climate.