Introduction: The burden of Tuberculosis (TB) in Africa continues to rise despite numerous interventions to stop the spread. Addressing factors associated requires a robust model that addresses cross-cutting issues in the continuum of TB care and management. The objective of this systematic review is to determine factors associated with poor treatment outcomes in newly diagnosed TB patients in sub-Saharan Africa. Method: The literature search identified 234 studies that were written in English. All the articles were identified via database search and imported into Mendeley for analysis. A total of 95 duplicates were removed and the abstracts of remaining studies were reviewed. A total of 139 abstracts were screened with misleading and non-open access journal articles removed. A full reading of the remaining 104 potentially relevant studies was done, in order to ascertain compliance with the inclusion/exclusion criteria and 24 studies were found to be eligible and were included in this review. Results: HIV co-infection, type of TB infection and gender were observed as most common factors associated with poor treatment outcomes in newly diagnosed patients. Several studies emphasized the impact of male gender on poor treatment outcomes stating a higher likelihood to developing unfavorable outcomes. Other factors identified included social factors namely employment, location, nutrition, failure to gain weight, failure to present at facility, delay to be treated at the facility and the type of facilities where one was treated. Conclusion: The common factors associated with poor treatment outcomes were HIV co-infection, type of TB infection and gender and these were notably underscored by social factors. Addressing these challenges will significantly improve the health outcomes of TB patients in the region.