The city of Villahermosa, a logistical center in the State of Tabasco’s economy, is affected by recurrent river floods. In this study, we analyzed the impact of two factors that are the most probable causes of this increase in flood hazard: changes in land use in the hydrological catchments upstream of the city, and the uncontrolled urbanization of the floodplains adjacent to the main river channels. Flood discharges for different return periods were evaluated, considering land uses of the catchments, both as they were in 1992 and as they are today. These flood discharges were then used in a 2D shallow water model to estimate the increase of water depths in the city from 1992 to the present day. To evaluate the influence of urban expansion on inundation levels, three future urbanization scenarios were proposed on the basis of the urban growth rate forecast for 2050. Results confirm that the change in land use in the hydrological catchments is the main factor that explains the increase in inundation events observed over recent years. This study also provides useful insights for future city planning that might help to minimize the flood impact on Villahermosa.