Southeastern South America (SESA) is a highly productive agricultural region and a hot spot for land-atmosphere interactions. To evaluate the impact of dry soil moisture anomalies (SMAs) on SESA climate and the sensitivity of the regional climate response to the location of SMAs, we perform three experimental simulations using the Community Earth System Model (CESM) with prescribed dry SMAs over (1) SESA, (2) western SESA, and (3) eastern SESA. The dry eastern SESA simulation shows widespread negative precipitation anomalies. In contrast, the dry western SESA simulation shows positive precipitation anomalies over northeastern Argentina, which are associated with the enhanced southward moisture flux co-located with the South American low-level jet exit region. A composite analysis of extremely dry cases over western SESA using reanalysis data agrees with the findings from our CESM experiment. These findings have potential implications for subseasonal forecasting in this region.