Climate variability is a major threat to maize (Zea mays) crops in Colombia, posing a risk to food security and compliance with Sustainable Development Goals. Therefore, this study aimed to assess the physical vulnerability of maize crops to climate variability in the semi-arid region of the Department of Cesar, Colombia, using the AquaCrop-OS model. Specifically, the study evaluated the vulnerability of maize crops to three typical meteorological years (dry, intermediate, and wet) adjusted to the growth cycle in two semesters of the year (periods I and II). An analysis of 43 years of data (1980–2022) revealed that most years in the area can be classified as intermediate, whereas the number of wet years was higher than the number of dry years. However, under the intermediate typical meteorological year scenario, maize cultivation in the department of Cesar experienced severe drought conditions during periods I and II. The study’s vulnerability curve showed an increasing rate within the yield loss index when the average water stress index was between 0.5 and 0.8 for period I. The rate of increase slowed when the index exceeded 0.9. For period II, the maize crop presented a lower degree of vulnerability, with 64% of the area experiencing a yield loss rate between 5% and 30%. The study also determined the required irrigation depth of water for optimal yields, which ranged from 70 to 160 mm during the growing season for all maize crop scenarios in the Department of Cesar. The results of this study can contribute to the consolidation of a database of physical vulnerability and threats of precipitation anomalies on regional and national scales. Overall, this study’s evaluation of the physical vulnerability of maize crops can help producers develop better strategies to mitigate the impacts of climate variability and ensure regional food security.