Background. Preventing the life of the newborn and reducing the entrenched disparity of childhood mortality across different levels is one of the crucial public health problems, especially in underdeveloped and developing countries in the world. Sustainable development goals (SDGs)-3.2 is aimed at terminating all preventable under-five child mortality and shrinking it to 25 per 1000 live births or lower than this by 2030. Several factors have been shown to be linked with childhood mortality. Objective. This review is aimed at pointing out the significant determinants related to under-five child mortality by a systematic review of the literature. Methods. EMBASE, PubMed, Scopus database, and Google Scholar search engine were used for the systematic search of the literature. Special keywords and Boolean operators were used to point out the relevant studies for the review. Original research articles and peer-reviewed papers published in the English language till August 10, 2022, were included in the analysis and synthesis of the results. As per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, out of 299 studies identified from different sources, only 22 articles were ascertained for this study. Eligible articles were appraised in detail, and relevant information was extracted and then integrated into the systematic review. Results. Mother’s education, size of child at birth, age of mother at childbirth, place of residence, birth interval, sex of child, type of birth (single or multiple), and birth order, along with other socioeconomic, maternal, child, health facility utilization, and community level variables, were observed as important covariates of under-five mortality. Conclusion. Women’s education and easy access to quality healthcare facilities should be the apex priority to lessen childhood mortality.