The Río de la Plata Grasslands region is one of the largest plains in the world, covering a significant portion of the southern Brazilian grasslands. This temperate sub-humid region is also one of the most diverse grassland areas globally. However, in the last decades, important land-use and land-cover changes occurred threatening the natural ecosystem and the provision of essential ecosystem services. In this chapter, we provide an overview of the primary land-use and land-cover changes that have occurred in this region over the last two decades. We also discuss some of the consequences derived from these changes on the ecosystem functioning, the supply of ecosystem services, and the human appropriation of primary production. Finally, we evaluate the observed transition trends among land-use and land-covers and speculate on the most likely changes that may occur in the next few years.