The impact of urbanization on lakes in the urban context has aroused continuous attention from the public. However, the long-term evolution of lakes in a certain megacity and the heterogeneity of the spatial relationship between related influencing factors and lake changes are rarely discussed. The evolution of 58 lakes in Wuhan, China from 1990 to 2019 was analyzed from three aspects of lake area, lake landscape, and lakefront ecology, respectively. The Multi-Scale Geographic Weighted Regression model (MGWR) was then used to analyze the impact of related influencing factors on lake area change. The investigation found that the total area of 58 lakes decreased by 15.3%. A worsening trend was found regarding lake landscape with the five landscape indexes of lakes dropping; in contrast, lakefront ecology saw a gradual recovery with variations in the remote sensing ecological index (RSEI) in the lakefront area. The MGWR regression results showed that, on the whole, the increase in Gross Domestic Product (GDP), RSEI in the lakefront area, precipitation, and humidity contributed to lake restoration. The growth of population and the proportion of impervious surface (IS) in the lakefront area had different effects on different lakes. Specifically, the increase in GDP and population in all downtown districts and two suburb districts promoted lake restoration (e.g., Wu Lake), while the increase in population in Jiangxia led to lake loss. The growth of RSEI in lakefront area promoted the restoration of most lakes. A higher proportion of IS in lakefront area normally resulted in more lake loss. However, in some cases, the growth of IS was caused by lake conservation, which contributed to lake restoration (e.g., Tangxun Lake). The study reveals the spatiotemporal evolution of multiple lakes in Wuhan and provides a useful reference for the government to formulate differentiated protection policies.