Antibiotics help in preventing and treating infections and increasing life expectancy globally. Globally, many people’s lives are being threatened by the emergence of antimicrobial resistance (AMR). The cost of treating and preventing infectious diseases has increased due to AMR. Bacteria can resist the effects of antibiotics by altering drug targets, inactivating drugs, and activating drug efflux pumps. According to estimates, five million individuals died in 2019 from AMR-related causes, wherein 1.3 million deaths were directly linked to bacterial AMR. Sub-Saharan Africa (SSA) experienced the greatest mortality rate from AMR in 2019. In this article, we discuss AMR’s causes and challenges SSA faces in implementing AMR prevention measures and propose recommendations to address the challenges. Antibiotic misuse and overuse, widespread usage in agriculture, and the pharmaceutical industry’s absence of new antibiotic development are the factors contributing to AMR. SSA’s challenges in preventing AMR include poor AMR surveillance and lack of collaboration, irrational use of antibiotics, weak medicine regulatory systems, lack of infrastructural and institutional capacities, lack of human resources, and inefficient infection prevention and control (IPC) practices. The challenges faced by countries in SSA can be addressed by increasing the public’s knowledge of antibiotics and AMR, promoting antibiotic stewardship, improving AMR surveillance, promoting collaboration within and beyond countries, antibiotics regulatory enforcement, and improving the practice of IPC measures at home, food handling establishments, and healthcare facilities.