Background Burnout is prevalent among medical students. Throughout their training, medical students face many psychosocial stresses that, if not managed, might cause burnout syndrome. Burnout could negatively impact students’ life and their academic performance. This study aims to estimate the prevalence of burnout among medical students at the College of Medicine, University of Kerbala, and assess factors associated with it. An analytic cross-sectional study. A sample of 424 students from all academic years from the College of Medicine, University of Kerbala, was approached. Data collection was conducted from June 11 to July 3, 2020, through a self-administered online questionnaire based on the Maslach Burnout Inventory Student Survey (MBI-SS). The MBI-SS included 15 questions with a 7-point rating ranging from 0 (never) to 6 (always). The tool measures three subscales: emotional exhaustion (5 questions), Cynicism (4 questions), and professional efficacy (6 questions). Statistical Package for the Social Sciences (SPSS) program version 24 was used for data analysis. Binary logistic regression was used to assess the association between burnout and students̓ variables, P value of a level < 0.05 considered statistically significant. Results The prevalence of burnout syndrome among medical students was 38.2%. About 85.6% of students had high emotional exhaustion, 77.8% had high cynicism, and 32.5% exhibited low professional efficacy. Female gender, regular use of legal substances, and family history of mental diseases were associated with significantly high rates of burnout. Conclusions Burnout is prevalent among medical students of the University of Kerbala with quite high levels of emotional exhaustion and cynicism and lower professional efficacy levels. Faculties of medicine need to consider burnout among their students and works to reduce unnecessary stresses by modifying and upgrading the educational and clinical environments.