This paper reviews more than 20 years of research about the Late Pleistocene and Early Holocene occupations of the Uruguayan plains. The aim of this synthesis is to provide an overview of the available information related to early human peopling of Uruguay. Here, we focus on the main issues discussed over the last two decades: early sites characterization and chronology, human response to climate change, cultural diversity, occupations patterns, mobility and technology. The systematic and continuous efforts made have provided new data and new perspectives regarding the earliest human occupations of the region. We have defined an archaeological complex landscape and ongoing research strategy is based on the three main types of site that compose it: residential camps, cave and rock shelters, and raw material sources. This has allowed us to expand and improve our understanding of the record. The new research and data provided by these sites have led us to propose a settlement model for the region and the period. A cultural diversity has been evidenced through in-depth studies of stratified archaeological sites, cultural sequence, a solid chronological database and lithic technology. Finally, we advance in the characterization of objects of social prestige among hunter-gatherers who occupied the plains during the end of the Pleistocene in Southeastern South America.