In low- and middle-income countries, data on antimicrobial use (AMU) and antimicrobial resistance (AMR) in aquaculture are scarce. Therefore, summarizing documented data on AMU, antimicrobial residue (AR), and AMR in aquaculture in Africa is key to understanding the risk to public health. Google Scholar, PubMed, African Journals online, and Medline were searched for articles published in English and French following the PRISMA guidelines. A structured search string was used with strict inclusion and exclusion criteria to retrieve and screen the articles. The pooled prevalence and 95% confidence intervals were calculated for each pathogen–antimicrobial pair using random effects models. Among the 113 full-text articles reviewed, 41 met the eligibility criteria. The majority of the articles reported AMR (35; 85.4%), while a few were on AMU (3; 7.3%) and AR (3; 7.3%) in fish. The articles originated from West Africa (23; 56.1%), North Africa (8; 19.7%), and East Africa (7; 17.1%). Concerning the antimicrobial agents used in fish farming, tetracycline was the most common antimicrobial class used, which justified the high prevalence of residues (up to 56.7%) observed in fish. For AMR, a total of 69 antimicrobial agents were tested against 24 types of bacteria isolated. Bacteria were resistant to all classes of antimicrobial agents and exhibited high levels of multidrug resistance. Escherichia coli, Salmonella spp., and Staphylococcus spp. were reported in 16, 10, and 8 studies, respectively, with multidrug resistance rates of 43.1% [95% CI (32.0–55.0)], 40.3% [95% CI (24.1–58.1)] and 31.3% [95% CI (17.5–49.4)], respectively. This review highlights the high multidrug resistance rate of bacteria from aquaculture to commonly used antimicrobial agents, such as tetracycline, ampicillin, cotrimoxazole, gentamicin, and amoxicillin, in Africa. These findings also highlighted the lack of data on AMU and residue in the aquaculture sector, and additional efforts should be made to fill these gaps and mitigate the burden of AMR on public health in Africa.