Mexico’s basin is one of the most altered in the country, owing to the presence of the megalopolis of Mexico City. Lake Texcoco, which had the basin’s biggest extension, dried up almost completely. The basin’s evolution over time led in the formation of a megabasin in which water is transported from one source to another to serve the urban region and subsequently drained to prevent flooding. The major hydrotechnical works in Mexico Basin have been interpreted as a solution to the problem of flooding in Mexico City, but they were actually part of a much larger strategy of territorial appropriation by the Spanish colonists. The ecological imbalance that has resulted has sparked a variety of social issues. For the purpose of analyzing the environmental transformation of Lake Texcoco over the last 500 years, actors and processes that influenced specific moments in the country’s history were identified; these elements showed the inexorable relationship between the lake and Mexico City. Subsequently, they were grouped by periods with similar trends in terms of the way in which society relates to and appropriates the natural environment of the lake. It was found that the critical moment for the desiccation of Lake Texcoco occurred during the Spanish colonial historical period as part of the redesign of the city; from then on, the same environmental imaginary prevailed century after century, shaped by social and economic factors. This study contributes to the literature on how urbanization affects natural resources by making an original theoretical contribution through an analysis based on political ecology, and it adds to the literature on how people use the prevailing federal area of the lake.