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Laguna Cabeza de Buey 2 is a multicomponent open air archaeological site located in the center of the Pampa grasslands (Buenos Aires province, Argentina). The results of several lines of evidence from the site (e.g., C-14 dating, geology, lithic technology, and zooarchaeology) are presented. These results enable the technological organization, subsistence strategies, and mobility and settlement patterns of hunter-gatherers that occupied the site and its relationship to environmental and climatic evolution to be studied. At least three pre-Hispanic occupation events (two in the Middle Holocene [6800 and 4150 years BP] and one in the Late Holocene) and one historical event were identified. Human occupations developed in relation to a shallow lake that evolved from the Middle Holocene during a climate similar to the present day, although more arid in early times. During the first occupation event lithic material comes exclusively from the Tandilia Mountain Range system, while subsequently source areas increase due to changes in mobility and social interactions, as does the diversity of knapping techniques. The guanaco was always the most important animal prey, complemented with pampas deer and three species of armadillo.