The objective of this paper is to explore the spatial distribution of industries in the innovation sector in Mexico. Through the use of Explanatory Spatial Data Analysis (ESDA), we aim to present an original study in a spatial context, in which the empirical analysis considers recently available firm-level geo-referenced data, as well as data from the Economic Census of 2009. We use global and local spatial statistics in order to identify, quantify, and locate spatial clusters of firms and their employment composition. By doing so, we aim to show the existence of "hot-spot" areas with strong dynamics of innovation activities. The analysis identifies the most innovative regions based on seven spatial clusters of large-size establishments across the country distributed primarily in urban and metropolitan areas. This study contributes to a better understanding of the prevailing conditions of innovation clusters in the country and may help in the design of specific innovation policies tailored to firm size and for specific sectors aiming to accelerate the regional innovation process. It also provides guidance to policymakers eager to promote the development of local economies and identify where regional innovation systems need to be developed, financed, and designed.