Lakes are one of the most important wetland types on the earth with many ecosystem functions. With continuing economic growth and climate change, lake abundance and surface areas throughout the world have been threatened by many factors, including by human and environmental disruptions. However, we still have limited knowledge on how human activities and climate change affect lake reductions and associated ecosystem services. Elucidating the underlying mechanisms of lake shrinkage will help maintain an ecological balance in urban planning, especially in rapidly developing countries. We explore the determinants of lake shrinkage and abundance reduction from the 1980s to the 2010s using remote sensing data of lakes in two large cities in eastern China: Nanchang and Shanghai. In order to account for the non-independence of time-series data, time series auto-regressive generalized least squares (GLS) models were used to examine the relationship between lake area/abundance and human activities and climate change. Our results show that human activities rather than climate change, are the most important determinants for the areas and numbers of lake shrinkage, and gross domestic product (GDP) and population size could explain more than half of the variation in the number and area of lakes with areas larger than 20 ha in the two cities. GDP and lake area shrinkage do not exhibit a linear relationship. This highlights the importance of wetland protection in the early development stage. Because the main determinants are human activities, cities have the ability to protect wetlands via suitable planning.