Synergistic combinations of climatic and land use changes have the potential to produce the most dramatic impacts on land cover. Although this is widely accepted, empirical examples, particularly involving deforestation in Latin America, are still very few. The geographic extent and causes of deforestation in subtropical seasonally dry forests of the world have received very little attention. This is especially true for the Chaco forests in South America, which are being lost at an alarming rate, sometimes higher than those reported for tropical forests. On this basis, the aims of this study were to analyze the changes in land cover that have occurred during the last three decades of the 20th century in the Chaco forests of central Argentina, and to explain the factors that have driven those changes. Results show major land cover changes. Approximately 80% of the area that was originally undisturbed forest is now occupied by crops, pastures, and secondary scrub. The main proximate cause of deforestation has been agricultural expansion, soybean cultivation in particular. This appears as the result of the synergistic convergence of climatic, technological, and socioeconomic factors, supporting the hypothesis of a multiple-factor explanation for forest loss, while providing one of the very few existing analyses of changes in subtropical forests of the world.