Background: Fascioliasis is a parasitic zoonosis that can infect humans and be a source of significant morbidity. The World Health Organization lists human fascioliasis as a neglected tropical disease, but the worldwide prevalence of fascioliasis data is unknown. Objective: We aimed to estimate the global prevalence of human fascioliasis. Data sources and methods: We performed a systematic review and prevalence meta-analysis. We used the following inclusion criteria: articles published in the English, Portuguese, or Spanish languages from December 1985 to October 2022 and studies assessing the prevalence of Fasciola in the general population with an appropriate diagnostic methodology, including longitudinal studies, prospective and retrospective cohorts, case series, and randomized clinical trials (RCTs). We excluded animal studies. Two reviewers independently reviewed the selected studies for methodological quality, performing critical standard measures from JBI SUMARI. A random-effects model was conducted of the summary extracted data on the prevalence proportions. We reported the estimates according to the GATHER statement. Results: In all, 5617 studies were screened for eligibility. Fifty-five studies from 15 countries were selected, including 154,697 patients and 3987 cases. The meta-analysis revealed a pooled prevalence of 4.5% [95% confidence interval (CI): 3.1–6.1; I2 = 99.4%; T2 = 0.07]. The prevalence in South America, Africa, and Asia was 9.0%, 4.8%, and 2.0%, respectively. The highest prevalence was found in Bolivia (21%), Peru (11%), and Egypt (6%). Subgroup analysis showed higher prevalence estimates in children, in studies from South America, and when Fas2-enzyme-linked immunosorbent assay (ELISA) was used as a diagnostic method. A larger study sample size (p = 0.027) and an increase in female percentage (p = 0.043) correlated with a decrease in prevalence. Multiple meta-regression showed a higher prevalence for hyperendemic than hypoendemic (p = 0.002) or mesoendemic (p = 0.013) regions. Conclusion: The estimated prevalence and projected disease burden of human fascioliasis are high. Study findings support that fascioliasis continues to be a globally neglected tropical disease. Strengthening epidemiological surveillance and implementing measures to control and treat fascioliasis is imperative in the most affected areas.