Objectives To determine the prevalence of and the risk factors associated with burnout and stress for medical students in Saudi Arabia. Methods A cross-sectional, survey-based study was distributed between January and February 2018 among all 500 medical students from the first to fifth years in a medical college; 356 of the students responded (71.2% response rate). Burnout was measured using the Maslach Burnout Inventory-Student Survey (MBI-SS) while the stress level was measured using the 12-item General Health Questionnaire (GHQ-12). Socio-demographics, professional characteristics, and participation in extracurricular activities were also included as possible predictors of burnout and stress. Results The study revealed that the stress level was (51.7%, n= 184) and the rate of high burnout was (38.2%, n= 136), expressing high exhaustion (77.8%, n=277), high cynicism (65.7%, n=234), and low academic efficiency (45.5%, n=162). Half of the students (50%, n=178) participated in extracurricular activities and were involved in one or more activities such as organizing activities and medical volunteering (n = 52, 14.6%), research (n = 59, 16.6%), and physical exercise (n = 71, 10.4%). There was a statistically significant positive correlation between overall burnout and a lower grade point average (GPA) (OR = 0.581, p 0.004, 95% CI = 0.400 to 0.843). A statistically significant positive correlation was found between stress and students with a lower GPA (OR = 0.737, P = 0.0.23, 95% CI = 0.566 to 0.959); stress was also higher in students who were not involved in any extracurricular activities (OR 1.893, P = 0.004, 95% CI = 1.22 to 2.918). Conclusion Our study shows high burnout rates among medical students. Low GPA students in this study showed a higher overall burnout. Stress was high in our study participants and was higher in students with a low GPA and in students who were not involved in any extracurricular activities.