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Climate changes and human activities can influence lake sediments, which may lead to disruptions in aquatic environments. A better understanding of these effects is crucial for the future management of lakes and reservoirs. The impacts of climate change and human activity factors, such as air temperature, land use patterns, population size, and gross domestic product (GDP), on lake sediments in China were considered in this study. A generalized additive model (GAM) was applied to quantitatively assess the relationships among climate change, human activities, and sediment variables, namely, total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP), in Lake Chaohu and Lake Chenghai. Both lakes are located in climate-sensitive areas, where the annual average temperature has risen by more than 1 degrees C over the past three decades. The impacts of climate changes and human activities on TOC, TN, and TP were quantitatively interpreted with the results of the GAMs. The results indicated that the contributions of air temperature to the variations in the sediment variables were significant but smaller than the contributions of human activities (e.g., percent of urban and paddy land, population size, and GDP) in both lakes. The fits of all GAMs were better than the fits of the stepwise linear regression comparisons. These findings demonstrate that GAMs are an effective tool for estimating the impacts of climate change and human activities on TOC, TN, and TP in lake sediments, suggesting that policy makers must further consider climate change when making management plans for water quality.