Abstract Introduction The COVID-19 pandemic substantially disrupted higher education by limiting in-person training and accelerating the transition to virtual learning. During the 2022 mpox outbreak, concerns emerged about the possibility of renewed academic disruption among university students. Objective To assess factors associated with perceived academic disruption in the event of a future pandemic among Latin American university students, with particular attention to country-level differences. Methods We conducted a multicountry cross-sectional analytical study using an online survey administered between July and August 2022 in several Latin American countries. The primary outcome was expected academic disruption, defined as reporting that studies would decrease or stop completely in the event of a future pandemic. A secondary outcome assessed high perceived academic impact, defined as reporting high or very high academic repercussions. Crude and adjusted prevalence ratios were estimated using generalized linear models with Poisson distribution, log link, and robust variance. Results Among 1,018 students, 75.1% expected that their studies would decrease or stop completely in the event of a future pandemic, and 73.6% perceived that the academic impact would be high or very high. In the adjusted model for the primary outcome, expected academic disruption was more frequent among students from Colombia (aPR: 1.15; 95% CI: 1.01–1.32; p=0.038) and less frequent among students from Bolivia (aPR: 0.83; 95% CI: 0.70–0.98; p=0.030), while increasing age was associated with a lower prevalence of expected disruption (aPR: 0.98; 95% CI: 0.97–0.99; p=0.004). Sex, type of university, field of study, and dichotomized concern about mpox were not independently associated with the primary outcome. In the secondary analysis, high perceived academic impact was associated with Colombia, sex, age, medical studies, and concern about mpox. Conclusions Expected academic disruption in the event of a future pandemic was frequent in this multicountry sample of Latin American university students and varied by country and age. Higher perceived intensity of academic impact was additionally associated with sex, medical studies, and concern about mpox. These findings may inform preparedness strategies to support academic continuity during future public health emergencies.