Background Breast cancer remains the most common cancer disease in the world. Higher breast cancer incidence and poor survival is also seen in different African countries. Diagnosed with breast cancer and treatment is a very stressful event that greatly diminished the quality of life of the patient. Therefore, the aim of this review was to assess health related quality of life and its determinants among breast cancer patients in Africa. Methods A systematic search of literatures was conducted from August 10 to September 5, 2020 without limitation of publication year in PubMed, HINARI, Science direct and Google scholar. The review followed PRISMA guidelines. Data were extracted in a well prepared Microsoft excel and exported to open meta-analysis software for analysis. The methodological quality of included studies was assessed based on 14 item modified quality of life assessment checklist. The pooled estimate quality of life scales were analyzed by open Meta analyst software and presented with forest plot. The results of included studies which were not suitable for meta-analysis were synthesized narratively. The heterogeneity of included studies was evaluated with I2 statistics. Results A total of ten studies which reported 2,190 breast cancer patients were included in the systematic review and meta- analysis. This review summarized five different standard instruments that used to measure health related quality of life. The pooled estimates mean score of general quality of life based on EORTC QLQ-C30 standard tool was 52.77 (95% CI: 42.199 to 63.345; I2 = 99.21%, P < 0.001). Age, level of education, marital status and financial difficulties were determinants health related quality of life in breast cancer patients in Africa. Conclusions The general health related quality of life of African breast cancer patients was not good. Therefore, more attention must be paid to the quality of life of breast cancer patients along with proper access to treatment. Protocol registration: The study protocol is registered at PROSPERO with reference ID CRD42020213726 and available at https://www.crd.york.ac.uk/prospero/displayrecord.php?id=crd42020213726