Wetlands provide critical habitat for birds and endangered species, and can be influenced by shifts in water availability and land use. The Landsat image archive can help both document historical wetland change and monitor current dynamics, but multi-decadal retrospective studies face two important challenges: 1) many important ecohydrological processes occur at scales finer than the field of view of a 30 m Landsat pixel, and 2) ecologically meaningful wetland response units frequently exhibit spatiotemporal complexity in both vegetation and surface water which may not be well-represented by a simple study area spatial mean. Here we explore a novel method for contending with these challenges with application to the rapidly changing Andrade Mesa wetlands along the US-Mexico border. Using a 26-year (1995–2021) Landsat image time series, we track changes in surface water and vegetation using green vegetation (V) and dark (D) fractions estimated from spectral mixture analysis (SMA). Spatiotemporal dynamics in both V and D fractions were characterized using two techniques: linear Principal Component Analysis (PCA) and nonlinear manifold learning (via Uniform Manifold Approximation and Projection; UMAP). Bounding temporal endmembers were identified from PCA and used to construct a temporal mixture model which quantified total area of surface water and vegetation loss, including an uncertainty estimate. UMAP clearly distinguished areas with differing onset of vegetation and water loss which were not identifiable using PCA. Change maps were then associated with different mechanisms and outcomes, including possible mechanical clearing of vegetation and unexpected greening of woody vegetation. The overall timing of surface water and vegetation decline follows the lining of the All-American Canal, suggesting a potential cross-border hydrologic association between loss of a wetland in Mexico and water efficiency measures implemented in the United States.