Land-use changes (LUC) are one of most significant global change processes of the current era, with noticeable consequences on habitat loss, due mainly to agricultural expansion and urbanization. The carbon cycle dynamics can be affected significantly by LUC, with impacts on carbon sequestration and emission rates. Considering the direct effect of carbon gases enrichment of the atmosphere on climate change, it is of utmost importance to improve the knowledge base on the impacts of agricultural-based LUC on carbon sinks, such as soils. This chapter reviews the available data on the effects of LUC on soil carbon stocks in three major biomes of the southern portion of the South American continent (the Cerrado, the Southern Grasslands and the Atlantic Forest). The area of soybean crops has expanded almost four times in the La Plata Basin Grasslands of Argentina over the past decade, and near ten times in the Brazilian Cerrado since the mid-1980s. The area under sugarcane crops in Brazil has almost doubled since the mid-1990s, occupying approximately 8.5 million ha (Mha) in 2009. In 2011, forestry plantations occupied 28% more land in Brazil than in 2005, with a total area of 6.5 Mha (75% with Eucalyptus and 25% with Pinus). In general, all conversions of natural vegetation to agricultural land-use systems in the different biomes have resulted in significant losses of soil carbon stocks. The conversion of pastures and grasslands to annual croplands in the Rolling Pampas grasslands has decreased C stocks by 50% over the last century. This represents a much faster loss rate than the loss triggered by the introduction of domestic herbivores over the course of the previous nearly four centuries (22%). These results imply that soil degradation caused by annual crops is very rapid and results in a strong decrease in carbon stocks. However, adopting soil and water conservation management strategies and increasing the complexity of the cropping systems - through adoption of no-tillage (NT) agriculture, well-managed pasture systems, integrated crop-livestock-forestry systems, multiple cropping and crop rotation with legume cover species, for example, can improve soil carbon sequestration rates by up to nearly 2.0 Mg C ha-1 year-1. The elimination of preharvest burning practices in sugarcane crops alone can result in gains of up to 0.93 t C year-1 ha-1. Improving soil and crop management to boost carbon sequestration in agricultural systems, while at the same time increasing resilience by improving soil quality, is a potential climate change mitigation option for farmers in South America.