The middle and lower reaches of the Yangtze River basin have the most representative and largest concentration of freshwater lakes in China. However, the size and number of these lakes have changed considerably over the past century due to the natural and anthropogenic impact. The lakes, larger than 10 km(2) in size, were chosen from relief maps and remotely sensed images in 1875, 1950, 1970, 1990, 2000, and 2008 to study the dynamics of lakes in the middle and lower reaches of the Yangtze River basin and to examine the causes and consequences of these changes. Results indicated that there was a dramatic reduction in lake areas, which decreased by 7,841.2 km(2) (42.64 %) during the study period (1875-2008), and the number of lakes in this region changed moderately. Meanwhile, a large number of lakes in the middle and lower reaches of the Yangtze River basin were directly converted into paddy fields, ponds, building lands, or other land-use types over the study period. Therefore, all kinds of lake reclamation should be identified as the major driving factors for the loss of lake in this region. Furthermore, flooding, soil erosion, and sedimentation were also the main factors which triggered lake changes in different periods. Some wetland conservation and restoration projects have been implemented since the 1970s, but they have not reversed the lake degradation. These findings were of great importance to managers involved in making policy for the conservation of lake ecosystems and the utilization of lake resources.