This paper addresses the diversification of plant resource management practices in the lowlands of southeastern Uruguay starting in the fourth millennium B.P. Our approach includes (a) a reexamination of ethnohistorical sources; (b) a review of lithic and ceramic materials; (c) the presentation of new ethnoarchaeological information; and (d) the analysis of starch grains from grinding stones. The results highlight the importance of the palm Butia odorata as a source of food and useful materials for much of the year. Furthermore, the analysis of both macro- and micro-residues has enabled us to identify the presence of Datura ferox seeds and starch grains from edible plants. While many of these identifications confirm the use of a number of previously reported species, others are new, as is the case with Phaseolus sp., Arachis sp., and Typha domingensis. Continuity in the management of certain plant species and in environmental conditioning is interpreted as an important investment in the long-term cycles of human-environment interactions.