Systematic review and meta-analysis were conducted to provide comprehensive information on the prevalence of amphistome infections in domestic ruminants in sub-Saharan Africa. A systematic search of peer-reviewed articles published between 2002 and 2023 was conducted. Prevalence estimates and meta-analysis were based on 76 peer-reviewed articles which met the inclusion criteria. Of the 55,122 domestic ruminants screened, 12,858 were infected, and the overall pooled prevalence was 22% (95% confidence interval [CI], 10-37). The highest prevalence was recorded in southern Africa 25% (95% CI, 0-62), and central Africa 16% (95% CI, 0-61) the lowest. Cattle were the most frequently sampled hosts (76.56%, n = 42,202) and sheep (8.78%, n = 4838) the lowest, and cattle recorded the highest pooled prevalence of 28% (95% CI, 12-47), and goats the lowest at 5% (95% CI, 0-14). Prevalence rate was the high in males 32% (95% CI, 21-44), adult ruminants 37% (95% CI, 15-62) and animals with poor body condition 47% (95% CI, 34-60), and during the wet season 36% (95% CI, 0-94). The highest pooled prevalence was recorded at postmortem 23% (95% CI, 8-43) compared to coprology 20% (95% CI, 6-39) studies. The meta-regression model demonstrated that the body condition score, host, and period, and the interactions of different factors significantly influenced the prevalence. The lowest prevalence rate was noted for the period between 2013 and 2023. This is the first systematic review and meta-analysis in sub-Saharan Africa that provides a comprehensive review of the prevalence of amphistome infections in domestic ruminants in the past 20 years.