Based on the optimized random forest (ORF) model proposed in our research, data of the Landsat-OLI, Landsat-TM images, and digital elevation model were used by us to obtain the land cover maps during several periods in the Napahai Basin. Model performance testing results show that producer accuracy and kappa coefficient of the ORF approach are 0.916 and 0.903, which are higher than the traditional maximum likelihood method. Furthermore, we analyzed the characteristic of land cover dynamic change and seasonal variation of wetlands landscape in 2002 and 2017, and revealed their driving mechanisms and ecological response process. The conclusions are as follows: (1) Lake area expanded in the past 15 years because of increased glacial runoff generated from global warming. Construction land and farmland replaced wetland areas in the middle and downstream regions. Moreover, due to the limitation of hydrothermal conditions in the canyon, few forests in the northeastern basin transferred to shrubs. (2) Dam, which was constructed in northern Napahai lake, controls water storage and made the lake area stable after 2013, so, area change percentage in 2017 from wet to dry season is lower than 2002. The wetland region in the central and downstream basin was synthetically affected by climate change and drainage projects, so its environment condition becomes dryer, and vegetation communities’ succession shows a reversed process. (3) Ecological problems in the Napahai Basin were mainly reflected at aspects of agricultural nonpoint source pollution, overgrazing, and urbanization. These factors affected lake, soil, and groundwater in the Napahai Basin and destroyed the ecological health of wetland landscapes. Therefore, in order to realize sustainable development environmental resources, local government should propose the effective policies to restore the degraded ecosystem and protect natural wetland.