Africa’s biodiversity sustains ecosystems, supporting humans, animals, plants, and the environment. It is, however, increasingly facing pressure, justifying the need for an integrated One Health approach that addresses human, animal, plants, and environmental health holistically. Additionally, the role of genomics and bioinformatics in One Health, especially in the context of food security, agriculture, environment and biodiversity conservation, has been underutilized. The African BioGenome Project (AfricaBP) has, since 2022, been raising awareness on the importance of genomics and bioinformatics in biodiversity conservation, preservation, and sustainable use and innovations. Through its AfricaBP Open Institute, the project promotes knowledge sharing and scientific entrepreneurship, and strengthens data sovereignty. In 2025 the AfricaBP Open Institute held 45 workshops across 12 African countries, training 545 African researchers in various skills, including genome sequencing, bioinformatics analysis, molecular biology, sample collection, biobanking, ethical, legal and social aspects of genetic resources, and attracted 4980 registered participants across 75 countries worldwide. Here, we provide a status update on One Health approaches in Africa, scanning various implementation models adopted at national, regional, and continental levels. We also underscore the importance of implementing African One Health strategies using biodiversity genomics and bioinformatics as tools. Finally, we propose a set of recommendations such as establishing more national One Health strategic plans and networks funded and governed through national and local funding mechanisms to focus on actualising national and regional priorities, establishing integrated Pan-African One Health Framework for Biodiversity Genomics and Bioinformatics to drive sustainable conservation conservation and food security, better connect socio-economics and policy issues. Finally, we provide insights into how biodiversity genomics and bioinformatics could be leveraged to inform One Health policies through quantitative and qualitative sequence data and information.