Lakes are considered sentinels of terrestrial environmental change. Nevertheless, our understanding of the impact of catchment anthropogenic activities on nutrients and the partial pressure of carbon dioxide (pCO2, an important parameter in evaluating CO2 levels in water) is still restrained by the scarcity of long-term observations. In this study, spatiotemporal variations in nutrient concentrations (total nitrogen: TN, total phosphorus: TP, nitrate: NO3−–N, and ammonium: NH4+–N) pCO2 in Taihu Lake were analyzed from 1992 to 2006, along with the gross domestic product (GDP) and wastewater discharge (WD) of its catchment. The study area was divided into three zones to characterize spatial heterogeneity in water quality: the inflow river mouth zone (Liangxi River and Zhihugang River), transition zone (Meiliang Bay), and central Taihu Lake, respectively. It is abundantly obvious that external nutrient inputs from the catchment have a notable impact on the water parameters in Taihu Lake, because nutrient concentrations and pCO2 were substantially higher in the inflow river mouth zone than in the open water of Meiliang Bay and central Taihu Lake. The GDP and WD of Taihu Lake’s catchment were significantly and positively correlated with the temporal variation in nutrient concentrations and pCO2, indicating that catchment development activities had an impact on Taihu Lake’s water quality. In addition, pCO2 was negatively correlated with chlorophyll a and the saturation of dissolved oxygen, but positively correlated with nutrient concentrations (e.g., TN, TP, and NH4+–N) in inflow river mouth zone of Taihu Lake. The findings of this study reveal that the anthropogenic activities of the catchment not only affect the water quality of Taihu Lake but also the CO2 concentrations. Consequently, catchment effects require consideration when modeling and estimating CO2 emissions from the extensively human-impacted eutrophic lakes.