Journal of Medical Entomology, XX(X), pp. 1–45African animal trypanosomiasis (AAT) a parasitic disease of livestock in sub-Saharan Africa causing tremen- dous loses. Sub-Saharan continental estimation of mean prevalence in both large and small domestic animals, risk factors, tsetse and non-tsetse prevalence and drug resistance is lacking. A review and meta-analysis was done to better comprehend changes in AAT prevalence and drug resistance. Publish/Perish software was used to search and extract peer-reviewed articles in Google scholar, PubMed and CrossRef. In addition, ResearchGate and African Journals Online (AJOL) were used. Screening and selection of articles from 2000–2021 was per- formed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles 304 were retrieved; on domestic animals 192, tsetse and non-tsetse vectors 44, risk factors 49 and trypanocidal drug resistance 30. Prevalence varied by, host animals in different countries, diagnostic methods and species of Trypanosoma. Cattle had the highest prevalence with Ethiopia and Nigeria leading, T. congolense (11.80– 13.40%) and T. vivax (10.50–18.80%) being detected most. This was followed by camels and pigs. Common di- agnostic method used was buffy coat microscopy. However; polymerase chain reaction (PCR), CATT and ELISA had higher detection rates. G. pallidipes caused most infections in Eastern regions while G. palpalis followed by G. mortisans in Western Africa. Eastern Africa reported more non-tsetse biting flies with Stomoxys leading. Common risk factors were, body conditions, breed type, age, sex and seasons. Ethiopia and Nigeria had the highest trypanocidal resistance 30.00–35.00% and highest AAT prevalence. Isometamidium and diminazene showed more resistance with T. congolense being most resistant species 11.00–83.00%.