The Andean plateau is a small region of South America extending between northwest Argentina, southwest Bolivia, and northern Chile. It concentrates the largest global resources of lithium brines in its numerous salars. Of these, the giant salars in Bolivia and Chile have been relatively well studied; however, only little is known about the smaller but numerous salars in the Argentine Puna region. In this article, we present the results of the first regional-scale reconnaissance exploration of the 12 major salars situated in the southern part of the Puna plateau (24°S–26°30’S). Hydrochemical data indicate that the shallowest brines are characterized by highly variable Li concentrations, with mean Li grades ranging between 57 and 570 mg L−1, and mean Li/Mg ratios from 0.01 to 1.24. A survey of the brine chemistry of the salars across the Puna plateau, including its northern part, has revealed the absence of a geographical pattern in Li+ grade distribution. However, a comparison among mean Li+ grades, Li+/Mg2+ ratios, and the sizes of all salars allows an estimation of their Li mining potential. Specifically, the salt pan of Arizaro represents the highest potential, mainly due to its size; Antofalla-Botijuelas has a large surface and promising Li/Mg ratios for Li recovery via brine evaporation, though its elongated shape is a constraint; and Pastos Grandes, Pozuelos, and Rincón have encouraging Li grades, interesting salar sizes, and relatively easy access. Olaroz, Cauchari, and Hombre Muerto contain the highest Li+ grades in brines of the Argentine Puna and embody the most interesting perspectives of the Argentine plateau in a regional context. Salar sizes could be related to maximum Li+ grade of brines. Larger salars would then be expected to contain brines with higher Li+ grades than smaller ones, which could be considered as a useful criterion for surveys of brine-type deposits.