Climate change has caused inland wetlands shrinkage and exacerbated problems, such as sustainable development and ecological security, for years. These issues are mainly pronounced in the inland arid area. The ecological environment’s deterioration is especially severe in the drylands of the interior. However, dryland wetland changes and their response to climate are poorly understood. This study uses the K-means algorithm in Google Earth Engine (GEE) to classify two typical dryland wetlands (Ebinur and Bosten Lakes) for rapidly and accurately detecting dryland wetland changes. Moreover, it explores the long-term spatial–temporal variation in wetland distribution. In addition, it investigates the response of various lakes to climate change in northern and southern Xinjiang using wavelet analysis. The study’s results showed that K-means clustering in the GEE platform has a high classification accuracy (Kappa > 0.8) in wetland classification, making it a feasible approach. The terminal lake wetland types, represented by the Ebinur Lake, changed significantly between 2001 and 2021. In contrast, the inflow-outflow lake wetland types, represented by the Bosten Lake, perform more consistently. Significant spatial–temporal variation is observed at Ebinur Lake, with the lake gradually shrinking and transforming into a marsh, where the largest marsh proportion degrades into non-wetland during the year. Bosten Lake experienced frequent conversions between marsh and non-wetland throughout the year. Furthermore, the responses of various dryland lakes to climate change are consistent, and a low precedes precipitation and follows evapotranspiration. However, their sensitivity to climate response varies, with the terminal lake being most affected by climate change. Mastering the dynamic changes and climate response of dryland wetlands achieves the sustainable development goals of drylands, including carbon neutrality and peak carbon dioxide emissions.