Optimal adherence to antiretroviral therapy (ART) remains the bedrock of effective therapy and management of human immunodeficiency virus (HIV). This systematic review examines the effect of interventions in improving ART adherence in sub-Saharan Africa (SSA), which bears the largest global burden of HIV infection. In accordance with PRISMA guidelines, and based on our inclusion and exclusion criteria, PUBMED, MEDLINE, and Google Scholar databases were searched for published studies on ART adherence interventions from 2010 to 2019. Thirty-one eligible studies published between 2010 to 2019 were identified, the categories of interventions were structural, behavioral, biological, cognitive, and combination. Study characteristics varied across design, intervention type, intervention setting, country, and outcome measurements. Many of the studies were behavioral interventions conducted in hospitals with more studies being randomized controlled trial (RCT) interventions. Despite the study variations, twenty-four studies recorded improvements. Notwithstanding, more quality studies such as RCTs should be conducted, especially among key affected populations (KAPs) to control transmission of resistant strains of the virus. Reliable objective measures of adherence should replace the conventional subjective self-report. Furthermore, long-term interventions with longer duration should be considered when evaluating the effectiveness of interventions.