Expanding urbanization in highly fragile desert environments requires a thorough understanding of the current state and trends of land uses to achieve an optimal balance between development and the integrity of vital ecosystems. The objectives of this study are to quantify land use change over the 25-year period 1990–2015 and analyze temporal and spatial urbanization trends in the Middle Rio Grande Basin. We conclude by indicating how the results can inform on-going water resource research and public policy discussion in an arid region. Results show that the predominant upland mixed vegetation land cover category has been steadily declining, giving up land to urban and agricultural development. Urban development across the region of interest increased from just under three percent in 1990 to more than 11 percent in 2015, mainly around the major urban areas of El Paso, Ciudad Juárez, and Las Cruces. Public policy aspects related to results from this study include transfer of water rights from agriculture to land developers in cities, higher risk of flooding, loss of natural ecosystems, and increased water pollution from point and non-point sources. Various stakeholders can find the study useful for a better understanding of historical spatial and temporal aspects of urban development and environmental change in arid regions. Such insights can help municipal authorities, farmers, and other stakeholders to strike a balance between development needs and protecting vital ecosystems that support the much needed development, especially in regions that are endowed with transboundary natural resources that often are incompletely represented in single nation data.