Assessing the impact of climate change and anthropogenic activity on Florida coastal areas requires a thorough understanding of natural climate variability. The available instrumental record, however, is too short and too limited to capture the full range of natural variability. In order to provide additional data on the natural state of the climate system and to evaluate the influence of human impact, we reconstructed climatic and environmental changes of the past 300 years. Pre- (before 1900 ad) and post-human impact conditions were compared in Rookery Bay, a subtropical, southern Florida estuary and its bordering wetland system. Biomarkers from terrestrial and aquatic environments were used to reconstruct temperature, runoff, and aquatic productivity. Pre-anthropogenic conditions before 1750 ad indicate a relatively large contribution of mangrove-derived organic matter, locally decreasing at the end of this period. After 1750 ad follows a relatively stable period in which biomarker concentrations indicate relatively low levels of runoff and aquatic production. Enhanced anthropogenic activities, such as land clearance and hydrological alterations, end this period of stability by altering the hydrological conditions. This leads to a more dynamic system which is more sensitive to disturbances of vegetation and drainage, as evidenced by peak terrestrial biomarker fluxes during the twentieth century. These episodes of enhanced runoff resulted in eutrophication and algal blooms in Rookery Bay. Natural climate phenomena, such as a positive AMO phase and hurricane activity, might have added to ongoing processes during the twentieth century.