Phytoplankton productivity (PP) is expected to be impacted by climate change and anthropogenic activity in freshwater ecosystems, but the effects and interactions of these environmental stressors are often complex and not clearly understood. In this research, we investigated the influences of climate change and human activity on changes in PP recorded by sedimentary organic geochemical proxies (including bulk properties, Rock-Eval parameters, n-alkanols, and sterols) in the Pearl River Delta of southern China over the past few decades. Multiple proxies suggested that PP has increased in the mesotrophic Lian'an reservoir (LA) and the eutrophic Liuhuahu lake (LHH) since the 1960s. Phytoplankton sterols revealed that the dominant algal community consisted of dinoflagellates, cyanobacteria, and green algae in LA, while cyanobacteria and green algae were the primary algae groups in LHH. Phytoplankton proxies exhibited significant positive correlation with rising temperature (r > 0.57, p < 0.05) and nutrient loadings (r > 0.80, p < 0.01), suggesting that climate warming and nutrient input have contributed to the variations in PP. Climate change has caused a rise in temperature and changes in precipitation, along with human activity such as agriculture, dam construction, and sewage input, have collectively impacted aquatic environments. The generalized additive model (GAM) was used to quantitatively analyze the impacts of climate change and anthropogenic activity on aquatic ecosystems. Results demonstrated the cumulative and synergistic effects of climate change and anthropogenic activity, and higher climatic influences observed after the 1990s. The synergistic effects led to algal blooms and restricted the growth of aquatic macrophytes, particularly in the eutrophic LHH. This has worsened eutrophication and resulted in an imbalance in aquatic ecosystems. In summary, this research emphasizes the interactions between climate change and anthropogenic activity, and PP variations in aquatic ecosystems and underscores the importance of studying these factors to comprehend the influence of environmental stressors.