The increasing demand for carbon-free energy in recent years has positioned hydrogen as a viable option. However, its current production remains largely dependent on carbon-emitting sources. In this context, natural hydrogen, generated through geological processes in the Earth’s subsurface, has emerged as a promising alternative. The present study provides the first national-scale assessment of natural dihydrogen (H2) potential in Uruguay by developing a catalog of potential H2-generating rocks, identifying prospective exploration areas, and proposing H2 systems there. The analysis includes a review of geological and geophysical data from basement rocks and onshore sedimentary basins. Uruguay stands out as a promising region for natural H2 exploration due to the significant presence of potential H2-generating rocks in its basement, such as large iron formations (BIFs), radioactive rocks, and basic and ultrabasic rocks. Additionally, the Norte Basin exhibits potential efficient cap rocks, including basalts and dolerites, with geological analogies to the Mali field. Indirect evidence of H2 in a free gas phase has been observed in the western Norte Basin. This suggests the presence of a potential H2 system in this area, linked to the Arapey Formation basalts (seal) and Mesozoic sandstones (reservoir). Furthermore, the proposed H2 system could expand exploration opportunities in northeastern Argentina and southern Brazil, given the potential presence of similar play/tramp.