The article represents the first contribution in which the economic impact of a group of nine Latin American universities is estimated, following a demand-based approach and a homogeneous methodology. The analyzed universities have different profiles depending on their ownership, size, age, or geographic location. Using the input-output methodology, the impacts derived from the expenditures and investments made by both the universities and their related agents are estimated. The results show significant impacts (up to 4% of the regional GDP, depending on the case), which extend across the entire national territory and all economic sectors. The study demonstrates that the economic and social impact is highly relevant, providing a substantial return, overall in universities with a high level of R+D+I activities.