Antimicrobial resistance (AMR) has emerged as a leading cause of death in the African region, surpassing fatalities from malaria, HIV, and TB. In response to this critical threat, the region has adopted the AMR Global Action Plan and the African Union Framework for Antimicrobial Resistance Control 2020 – 2025, which is tailored to meet the specific needs of African nations through a coordinated approach. While most countries in the region have developed and prioritized National Action Plans (NAPs) to tackle AMR, the overall response remains inadequate given the magnitude of the threat, which endangers human, animal, environmental, aquatic, and plant health. Africa bears a significant burden of infectious diseases, accounting for approximately 95% of malaria deaths, 70% of people living with HIV, and 25% of TB deaths globally. In 2019, AMR was linked to approximately 55,000 deaths from HIV, 30,000 from malaria, and 255,000 overall. Major drivers of AMR in the region include the overuse and misuse of antimicrobials in human and food systems, migration, suboptimal vaccination rates, and environmental contamination from hospital and pharmaceutical effluents. Additionally, there is a lack of access to quality-assured antimicrobials and diagnostics, compounded by inadequate knowledge about AMR. Unlike high-income countries, where indiscriminate antimicrobial use is the primary factor driving AMR, African countries face additional challenges, including a lack of access to clean and safe water, poor Water, Sanitation, and Hygiene (WASH) programs, inadequate infection prevention measures, and suboptimal vaccinations for preventable diseases. One in three hospitals in the region lacks clean, safe running water, and one in eight people defecate openly due to inadequate sanitation. Investments in WASH, infection prevention, and biosecurity could save approximately 700,000 lives annually. Addressing AMR in Africa requires a comprehensive, multi-sectoral approach involving the entire society. Sustainable access to antimicrobials, including antibiotics, vaccines, and therapeutics, is crucial, as lack of access leads to more morbidity and mortality than AMR itself. Support for the region should focus on preventing infections, strengthening health and food systems, developing human resources, ensuring sustainable access to diagnostics and therapeutics, and investing in laboratory infrastructure to support surveillance and data generation.