Background: Medical students are at a significant risk of experiencing psychological issues, such as burnout. Over the past few years, more studies have been conducted on this topic, producing different results. Aims: The purpose of this review was to determine the global pooled prevalence rate and risk factors associated with burnout and its components among undergraduate (pre-intern) medical students. Method: From inception until 30 November 2021, nine electronic databases were used for an electronic search. Using random-effects meta-analysis, we pooled the estimates using the DerSimonian-Laird method. The prevalence of burnout in medical students was the primary outcome of interest. Data were analyzed globally, by country, by research measure. Age and sex were examined as confounders using meta-regression analysis. Results: A random-effects meta-analysis of 42 studies involving 26,824 evaluating the prevalence of burnout in medical students showed an overall prevalence rate 37.23% [32.66%; 42.05%], Q = 2,267.15(41), p < .0001, τ2 = .42, τ = .65, I2 = 98.2%; H = 7.5. Prevalence of emotional exhaustion, depersonalization, and personal accomplishment were 38.08% [30.67%; 46.10%], 35.07% [26.74%; 44.41%], and 37.23% [32.66%; 42.05%], respectively. Variations were observed between countries and research measures. Age (older) and sex (female) were both significant predictors of burnout. Conclusion: The prevalence of burnout in medical students was estimated to be 37.23%. It is urgent that future studies serve as a basis for the development of prevention and treatment programs to prevent and treat burnout in students.