The objective of this study was to evaluate the relationship between intercellular spaces and leaf gas exchange and the effect of total intercellular space on the growth of maize and sorghum under water restriction. The experiments were conducted in a greenhouse in a 2 × 3 factorial arrangement (two plant types and three water conditions: field capacity (FC = 100%), 75%FC, and 50%FC) with 10 replicates. The lack of water was a limiting factor for maize because it showed reductions in leaf area, leaf thickness, biomass, and gas exchange parameters, while sorghum remained unchanged, maintaining its water-use efficiency. This maintenance was correlated with the growth of intercellular spaces in sorghum leaves because the increased internal volume led to better CO2 control and prevented excessive water loss under drought stress. In addition, sorghum had more stomata than maize. These characteristics contributed to the drought tolerance of sorghum, while maize could not make the same adjustments. Therefore, changes in intercellular spaces promoted adjustments to avoid water loss and may have improved CO2 diffusion, characteristics that are important for drought-tolerant plants.