The overall goal of GenPath Africa is to control pathogen infections in Africa. Our consortium of African and European investigators proposes to build on our collective experience in responding to SARS-CoV-2 to better diagnose, monitor and clinically manage current and future epidemics in Africa. We propose to expand genomics capacity to combat drug resistant HIV-1 and TB through precision medicine and by using genomic epidemiology to guide the public health response. GenPath Africa will also apply recent developments in wastewater and one health surveillance to detect emerging pathogens. Capacity development activities will include degree training in South Africa and the transfer of technology to the National Public Health Institute of Mozambique. The consortium’s objectives will be achieved by connecting the specialized genomics facilities of the Africa CDC Pathogen Genomics Initiative (Africa PGI) in South Africa and Kenya with African national public health institutes to translate scientific advances into public health actions. Long-term collaborations with Germany and Belgium will be leveraged to help achieve these objectives and make precision medicine and precision public health a reality in southern and East Africa. The consortium will also contribute to the long-term capacity building objectives of Africa PGI by contributing to harmonising training resources and collaboration with existing networks to ensure that all data are of high quality and available in public databases. GenPath Africa will advance the EDTCP3 work program by: i) providing researchers and public health professionals with skills in genomic epidemiology to better understand infectious disease epidemiology and drug resistance, ii) strengthening capability in southern and East Africa to rapidly respond to current and emerging epidemics, and iii) providing researchers with training to advance their scientific careers in Africa and establish themselves as scientific and public health leaders.