This 14-chapter unique masterpiece presents the AMR problem in African, addressing the various compartments of the One Health – humans, animals, and the environment, to illustrate the need for concerted efforts in the fight against AMR, especially in Africa. Authors from the four cardinal points present diverse aspects of AMR in Africa, starting with behavioural and social drivers of AMR in Africa. Antimicrobial stewardship in an African context is also discussed. AMR in humans is presented through studies on antibiotic-resistant neonates and nontyphoidal Salmonella infections and the clinical relevance of the genetics of viral resistance. Topics on AMR in mastitis, biosecurity in animal farming and the linkage between disinfectants and AMR are discussed. The environmental dimension of AMR is discussed, notably in the aquatic environment, and its implication for aquaculture and irrigation and using nanomaterials to treat polluted waters from such environments are highlighted. Finally, Africa’s rich floral diversity is portrayed as an eco-friendly and cost-effective approach to combat AMR. Hopefully, the work presented will spur greater collaboration between scientists, environmental, animal and human health practitioners, the general population, and policymakers to assimilate and implement the One Health approach to combating AMR, rather than working in silos on their various sectors