Water level, as a key indicator for the floodplain area, has been largely affected by the interplay of climate variability and human activities during the past few decades. Due to a nonlinear dependence of water level changes on these factors, a nonlinear model is needed to more realistically estimate their relative contribution. In this study, the attribution analysis of long-term water level changes was performed by incorporating multilayer perceptron (MLP) artificial neural network. We took the Taihu Plain in China as a case study where water level series (1954–2014) were divided into baseline (1954–1987) and evaluation (1988–2014) periods based on abrupt change detection. The results indicate that climate variables are the dominant driver for annual and seasonal water level changes during the evaluation period, with the best performance of the MLP model having precipitation, evaporation, and tide level as inputs. In the evaluation period, the contribution of human activities to water level changes in the 2000s is higher than that in the 1990s, which indicates that human activities, including the rapid urbanization, are playing an important role in recent years. The influence of human activities, especially engineering operations, on water level changes in the 2000s is more evident during the dry season (March-April-May (MAM) and December-January-February (DJF)).