Antimicrobial stewardship (AMS) interventions to improve antibiotic use are being implemented in Africa, but their impact is not fully known. The aim of this review was to estimate the effectiveness of interventions to improve antibiotic prescribing for hospital inpatients. Studies from PubMed, Embase, African Journals Online and Google Scholar were systematically searched from January 2010 to July 2022. Studies were included if they reported the impact of AMS interventions on outcomes of interest for hospital inpatients in Africa. Risk of bias was evaluated using the Cochrane Effective Practice and Organization of Care guidelines and the National Heart, Lung and Blood Institute tool. Findings were summarized in tables and meta-analyses were performed using random-effects models. A total of 28 studies were included, 89% being uncontrolled before and after studies. Most interventions employed were multi-faceted and found to be effective, evidenced by increased compliance, reduction in antibiotic utilization and cost, and slight reduction or no difference in mortality and length of hospital stay (LOS). Meta-analysis generated a relative risk of 0.82 [95% confidence interval (CI) 0.70–0.97] for mortality, and a standard mean difference of -0.30 (95% CI -0.41 to -0.19) for LOS. Generally, a decrease in resistance to most micro-organisms was observed. Despite an increase in the number of AMS studies conducted in Africa, the studies lack most of the quality design features for AMS studies. In conclusion, antimicrobial stewardship interventions are likely to be effective; however, efforts are still required to align the study design with the quality design features required for validity and to inform practice.