Aida Elargoubi, John M. Morobe, Jiro Yasuda, Madisa Mine, Faustinos T. Takawira, Jean-Jacques Muyembe Tamfum, Amal Souissi, Hela Karray, Dominique Goedhals, Michael Owusu, Mitoha O. Ayekaba, Pascale Ondoa, Bryan Fulbert Nkengfack Tegomoh, Daniel G. Amoako, Mathabo Mareka, Sameh Trabelsi, Dorcas Maruapula, Magalutcheemee Ramuth, Danny S. Park, Bamidele Soji Oderinde, Maitshwarelo I. Matsheka, Robert A. Kingsley, Philippe Dussart, Matthew Cotten, Hesham A. Elgahzaly, Oyewale Tomori, Arash Iranzadeh, Nicksy Gumede, Marta Giovanetti, Folarin Onikepe, Omoruyi E. Chukwuma, Nnaemeka Ndodo, Mba Nwando, Oladiji Femi, Sylvie L. Budiaki, Gemma L. Kay, Johnson C. Okolie, Saber Masmoudi, Okokhere Peter, Hlanai Gumbo, Sara H.A. Agwa, Mooko Sekhele, Imed Gaaloul, Sheila M. Mandanda, Enatha Mukantwari, Ngonda Saasa, Sanaâ Lemriss, Hellen Nansumba, Akano Kazeem, Upasana Ramphal, Carolyn Williamson, Belinda Louise Herring, Vagner Fonseca, Edidah M. Ong'era, Joana Q. Mends, Ahmed E Ogwell Ouma, Anika Vinze, Ahmad Sayed, Richard Phillips, Adewunmi M. Olubusuyi, Bourema Kouriba, Vivianne Gorova, John O. Gyapong, Tulio de Oliveira, Arnold W. Lambisia, Najla Kharrat, Wolfgang Preiser, Ojide Chiedozie Kingsley, Yenew K. Tebeje, Sherihane Aryeetey, Yaw Bediako, David A. Rasmussen, Wael H. Roshdy, Norosoa Harline Razanajatovo, Siham Elhamoumi, Sylvie van der Werf, Moussa Moïse Diagne, Claudia Daubenberger, Oshomah Cyril, Andrew J. Page, Uwanibe Jessica, Matoke-Muhia Damaris, Daniel J. Bridges, Sumir Panji, Mahjoub Aouni, Adnene Hammami, Simani Gaseitsiwe, Daniel Lule Bugembe, Gugu Maphalala, Kim Hae-Young, Mohamed K. Khalifa, Safietou Sankhe, Fabian H. Leendertz, Richard Njouom, Ousmane Faye, Kwabena O. Duedu, Jeffrey G. Shaffer, Tobias Schindler, Bankole Bolajoko, Cathrine Scheepers, Francisca M. Muyembe, Ajogbasile F. Victoria, Mirabeau T. Youtchou, Ayoade Femi, Amel Chtourou, Kefentse A. Tumedi, Adrienne A. Amuri, Joyce M. Ngoi, Etile Anoh, Richmond Gorman, Mohamed Abouelhoda, Ali Ahmed Yahaya, Paulo Arnaldo, Alexander J. Trotter, Lahcen Belyamani, Isaac Ssewanyana, Susan Nabadda, Arshad Ismail, Julia C. Andeko, James Emmanuel San, Susan Engelbrecht, Sikhulile Moyo, Jinal N. Bhiman, Jean-Michel Heraud, Julius J. Lutwama, Samar Metha, Amadou Diallo, Soa-Fy Andriamandimby, Rosina A. A. Carr, Edgar Simulundu, Steve A. Mundeke, Nelson B. Silochi, Shymaa S. Ahmed, Nadia Touil, Ihekweazu Chikwe, Deogratius Ssemwanga, Ilhem Boutiba-Ben Boubaker, Houriiyah Tegally, Okogbenin Sylvanus, Abdoul K. Sangare, Mulenga Mwenda, Fausta Shakiwa Mosha, Amadou A. Sall, Derek Tshiabuila, D. James Nokes, Yvan Butera, Maximillian Mpina, Adedotun-Sulaiman Kemi, Onwe E. Ogah, Jean B. Lekana-Douk, Stephen F. Schaffner, Vincent Enouf, Chantal Akoua-Koffi, Diarra Bassirou, Edwin Shumba, Deelan Doolabh, Saba Gargouri, Kayode T. Adeyemi, Wonderful T. Choga, Nicola Mulder, Inbal Gazy, Mushal Allam, Saâd El Kabbaj, Christian T. Happi, Frank Tanser, Sobajo Tope, Michael R. Wiley, Katherine J. Siddle, Charles N. Agoti, John Kayiwa, George Githinji, Diego F. Cuadros, Abdoul-Salam Ouédraogo, Fowotade Adeola, Sonia Lekana-Douki, Edith N. Ngabana, William Ampofo, U George, Elmostafa El Fahime, Jean-Claude C Makangara, Nalia Ismael, Ebenezer Foster-Nyarko, Samar K. Kassim, Nedio Mabunda, Hafaliana Christian Ranaivoson, Tapfumanei Mashe, Sylvie Behillil, Etienne Simon-Loriere, Donwilliams O. Omuoyo, Darren P. Martin, Azeddine Ibrahimi, Paul E. Oluniyi, Richard J Lessells, My V. T. Phan, Feriel Bouzid, Salako B. Lawal, Gert U. van Zyl, Fares Wasfi, Christophe Peyrefitte, Joyce Namulondo, Ugochukwu J. Anyaneji, Mariétou Faye Paye, Augustina Sylverken, Sébastien Calvignac-Spencer, Malebogo Kebabonye, Sophie J Prosolek, Mahmoud el Hefnawi, Adeyemi O. O. Oluwapelumi, Fakayode O. Enoch, Eddy Kinganda Lusamaki, Gaetan Thilliez, Beatrice Dhaala, Gabriel K. Mbunsu, Lavanya Singh, Nnennaya A. Ajayi, Justin O'Grady, Olawoye Idowu, Ngoy Nsenga, Baba Marycelin, Ndongo Dia, Abdul Karim Sesay, Ikponmwosa Odia, Chika K. Onwuamah, Pardis C. Sabeti, Collins M. Morang’a, Hajar Lemriss, Dominic S. Y. Amuzu, Jones Gyamfi, Sofonias K. Tessema, Iyaloo Konstantinus, Pontiano Kaleebu, Patrick Semanda, Fawzi Derrar, Alpha Kabinet Keita, Joweria Nakaseegu, Ibtihel Smeti, Jocelyn Kiconco, Audu Rosemary, K Said, Bronwyn Kleinhans, Fatma Abdelmoula, Sureshnee Pillay, Abechi Priscilla, Manel Turki, Fred A. Dratibi, Berthe-Marie Njanpop-Lafourcade, Zaydah R. de Laurent, David Baker, Nadine Rujeni, Oguzie Judith, Peter K. Quashie, Phillip Armand Bester, Emmanuel Lokilo, Catherine Pratt, Nabil Abid, Mamadou Diop, Placide Mbala, Eduan Wilkinson, Johnathan A. Edwards, Ahmed Rebai, Haruka Abe, Ana Victoria Gutierrez, Thanh Le-Viet, Essia Belarbi, Steven Rudder, Jouali Farah, Maha Mastouri, Nei-yuan Hsiao, Happi Anise, Cara E. Brook, Lamia Fki-Berrajah, Gordon A. Awandare, Ugwu Chinedu, Abdel-Rahman N. Zekri, Sami Kammoun, Leonardo de Oliveira Martins, Martin M. Nyaga, Lynn Tyers, Jingjing Li, Ikhlas Ben Ayed, Mouna Ouadghiri, Amadou Koné, Reuben Ayivor-Djanie, Innocent Mudau, Thabo Mohale, Olumade Testimony, Eromon Philomena, Yeshnee Naidoo, Patrice Combe, Seydou Doumbia, Anne von Gottberg, Akpede George, Nosamiefan Iguosadolo, Mohamed G. Seadawy, Bronwyn McInnis, Faida Ajili, Grit Schubert, Tarik Aanniz, Maureen W. Mburu, Soumeya Ouangraoua, John N. Nkengasong, Jennifer Giandhari, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Stellenbosch University, Laboratório de Biologia Molecular de Flavivírus [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cincinnati (UC), University of Cape Town, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), University of Chicago, Institut Pasteur de Madagascar, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Centre Hospitalier de Mayotte, Centre Pasteur du Cameroun, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Sfax - University of Sfax, National Institute for Communicable Diseases [Johannesburg] (NICD), University of the Witwatersrand [Johannesburg] (WITS), Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Centre for the AIDS Programme of Research [Durban, South Africa] (CAPRISA), University of Washington [Seattle], The University of Ghana (WACCBIP) team was funded by a Wellcome/African Academy of Sciences Developing Excellence in Leadership Training and Science (DELTAS) grant (DEL-15-007 and 107755/Z/15/Z: Awandare), National Institute of Health Research (NIHR) (17.63.91) grants using UK aid from the UK government for a global health research group for genomic surveillance of malaria in West Africa (Wellcome Sanger Institute, UK) and the global research unit for Tackling Infections to Benefit Africa (TIBA partnership, University of Edinburgh), and a World Bank African Centres of Excellent grant (WACCBIP-NCDs: Awandare). Project ADAGE PRFCOV19-GP2 (2020-2022) includes 40 researchers from the Center of Biotechnology of Sfax, the University of Sfax, the University of Monastir, the University Hospital Hédi Chaker of Sfax, the Military Hospital of Tunis, and Dacima Consulting. Ministry of Higher Education and Scientific Research and Ministry of Health of the Republic of Tunisia. The Uganda contributions were funded by the UK Medical Research Council (MRC/UKRI) and the UK Department for International Development (DFID) under the MRC/DFID concordat agreement (grant agreement number NC_PC_19060) and by the Wellcome, DFID–Wellcome Epidemic Preparedness–Coronavirus (grant agreement number 220977/Z/20/Z) awarded to M.C. Work from Quadram Institute Bioscience was funded by The Biotechnology and Biological Sciences Research Council Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348, BBS/E/F/000PR10349, BBS/E/F/000PR10351, and BBS/E/F/000PR10352 and by the Quadram Institute Bioscience BBSRC–funded Core Capability Grant (project number BB/CCG1860/1). The Africa Pathogen Genomics Initiative (Africa PGI) at the Africa CDC is supported by the Bill & Melinda Gates Foundation (INV018978 and INV018278), Illumina Inc, the US Centers for Disease Control and Prevention (CDC), and Oxford Nanopore Technologies. Sequences generated in Zambia through PATH were funded by the Bill & Melinda Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. Funding for sequencing in Côte d’Ivoire, Burkina Faso, and part of the sequencing in the DRC was granted by the German Federal Ministry of Education and Research (BMBF). Sequencing efforts from Morocco have been supported by Academie Hassan II of Science and Technology, Morocco. Funding for surveillance, sampling, and testing in Madagasar was provided by the WHO, the CDC (grant U5/IP000812-05), the US Agency for International Development (USAID, cooperation agreement 72068719CA00001), and the Office of the Assistant Secretary for Preparedness and Response in the US Department of Health and Human Services (DHHS, grant number IDSEP190051-01-0200). Funding for sequencing was provided by the Bill & Melinda Gates Foundation (GCE/ID OPP1211841), Chan Zuckerberg Biohub, and the Innovative Genomics Institute at UC Berkeley. The Botswana Harvard AIDS Institute was supported by the following funding: H3ABioNet through funding from the National Institutes of Health Common Fund (U41HG006941)—H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) program of the African Academy of Science (AAS), DHHS–NIH–National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928-04 and 5K24AI131924-04), Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-0060—the DELTAS Africa Initiative is an independent funding scheme of the AAS’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant 107752/Z/15/Z] and the UK government, and the South African Medical Research Council (SAMRC) and the Department of Technology and Innovation as part of the Network for Genomic Surveillance in South Africa (NGS-SA) and the Stellenbosch University Faculty of Medicine & Health Sciences, Strategic Equipment Fund. D.P.M. is funded by the Wellcome Trust (Wellcome Trust grant 222574/Z/21/Z). Sequencing activities at the NICD were supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response, a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the U.S. Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00), the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978, the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z), the South African Medical Research Council (Reference number SHIPNCD 76756), the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. Furthermore, pandemic surveillance in South Africa and Senegal was supported in part through NIH grant U01 AI151698 for the United World Antiviral Research Network (UWARN). Support for pandemic surveillance from the Tulio de Oliveira group to other African countries is funded by the Rockefeller Foundation. Sequencing efforts in the DRC were funded by the Bill & Melinda Gates Foundation under grant INV-018030 awarded to C.B.P. and further supported by funding from the Africa CDC through the ASLM (African Society of Laboratory Medicine) for Accelerating SARS-CoV-2 Genomic Surveillance in Africa. Sequencing efforts in Rwanda were commissioned by the NIHR Global Health Research program (16/136/33) using UK aid from the UK government (funding to E.M. and N.R. through TIBA partnership) and additional funds from the government of Rwanda through RBC/National Reference Laboratory in collaboration with the Belgian Development Agency (ENABEL) for additional genomic sequencing at GIGA Research Institute–Liege/Belgium. The sequencing effort in Equatorial Guinea was supported by a public-private partnership, the Bioko Island Malaria Elimination Project, composed of the government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon EG Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG. Sample collection and typing in Mali were supported by Fondation Merieux–France, and sequence efforts have been supported by the Enable and Enhance Initiative of the German Federal Government’s Security Cooperation against Biological Threats in the G5 Sahel Region. The Nigeria work was made possible by support from Flu Lab and a cohort of generous donors through TED’s Audacious Project, including the ELMA Foundation, MacKenzie Scott, the Skoll Foundation, and Open Philanthropy. Further Nigeria funding came from grants from the NIAID (www.niaid.nih.gov), NIH-H3Africa (https://h3africa.org) (U01HG007480 and U54HG007480), and the World Bank grant (worldbank.org) (ACE IMPACT project) to C.H. Analysis for the Gabon strains was supported by the Science and Technology Research Partnership for Sustainable Development (SATREPS), Japan International Cooperation Agency (JICA), and Japan Agency for Medical Research and Development (AMED) (grant number JP20jm0110013) and a grant from AMED (grant number JP20wm0225003). Sequencing at KEMRI-Wellcome Trust Research Programme site in Kenya was supported by the National Institute for Health Research (NIHR) (project references 17/63/82 and 16/136/33), using UK aid from the UK Government to support global health research, and the UK Foreign, Commonwealth and Development Office and Wellcome Trust (grant# 102975, 220985)., and We acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared, via GISAID, the genetic sequence data on which this research is based (table S4). We also acknowledge the contribution of K. Maria from the NGS-SA platform for their contribution toward the sequencing effort in Cape Town, South Africa. Similarly, we thank A. M. Elsaame, S. M. Elsayed, and R. M. Darwish from the Faculty of Medicine Ain Shams Research Institute (MASRI) for their efforts toward sequencing in Egypt. We thank S. Bane, M. Sanogo, D. Diallo, A. Combo Georges Togo, and A. Coulibaly from the University Clinical Research Centre (UCRC) at the University of Sciences, Techniques, and Technologies of Bamako for the contribution they have made toward sequencing efforts in Mali. We acknowledge the contribution of M. Moeti and A. Salam Gueye from the WHO for their contribution toward combating SARS-CoV-2 on the African continent. We further wish to extend acknowledgment to S. Lutucuta and J. Morais from the Angolan Ministry of Health for their continued hard work with regards to SARS-CoV-2 sampling, sequencing, and pandemic response in Angola. From Malawi we wish to acknowledge the work of B. Chilima, B. Mvula, and M. Chitenje from the Malawian Ministry of Health for their work on the COVID-19 response within the country.