Introduction: The spread of agricultural use leads to changes in vegetation cover, loss of biodiversity and ecosystem services. Objective: To analyze land use change and its effect on natural vegetation in the region of Los Ríos, Tabasco, Mexico, during the period 1947-2019. Materials and methods: A total of 14 land use and vegetation classes were identified using aerial photographs from 1947 and supervised classification of satellite images, verifying those from 1947 to 2000 with published cartography and those from 2019 (Landsat 8) in the field. Land use and vegetation cover change was analyzed by overlaying and comparing the maps with the Land Change Modeler module integrated in the TerrSet program. Results and discussion: In 72 years, natural vegetation was mostly replaced by crops, grassland and forest plantations, followed by human settlements. These uses, together, represented 14.2 % of the region’s surface and increased to 61.8 %; that is, an increase of 435 %. These uses replaced areas of rainforest, secondary vegetation and hydrophytes, which went from 82.3 % to 29.7 %, representing a loss of 64 % of these coverages. Between 1947 and 1984, natural vegetation suffered the greatest loss of area (53.7 %). Conclusions: The loss of natural vegetation in the region occurred because of the increase in agricultural land and human settlements. The increase in agricultural land was driven by government programs without considering the environmental factor.