We gratefully acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared via GISAID genetic sequence data on which this research is based (table S4). We also wish to acknowledge the contribution of Kruger Maria from the National Genomics Surveillance of South Africa (NGS-SA) platform for their contribution toward the sequencing effort in Cape Town, South Africa. Similarly, we wish to thank Aya M Elsaame, Shimaa M, Elsayed and Reham M. Darwish from the Faculty of Medicine Ain Shams Research institute (MASRI), for their efforts toward sequencing in Egypt. Sidy Bane, Moumine Sanogo, Dramane Diallo, Antieme Combo Georges Togo and Aminatou Coulibaly from the University Clinical Research Centre (UCRC), at the University of Sciences, Techniques and Technologies of Bamako we wish to extend our thanks for the contribution they have made toward sequencing efforts in Mali. Finally, we wish to acknowledge the contribution of Dr Matshidiso Moeti and Dr Abdou Salam Gueye from the World Health Organization for their contribution toward combating SARS-CoV-2 on the African continent. Funding: 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 global research unit for Tackling Infections to Benefit Africa (TIBA partnership, University of Edinburgh), and the 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 MC. 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 and Melinda Gates Foundation (INV018978 and INV018278), Illumina Inc, Center 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 Democratic Republic of the Congo 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: World Health Organization (WHO), the US Centers for Disease Control and Prevention (US CDC: Grant#U5/IP000812-05), the United States Agency for International Development (USAID: Cooperation Agreement 72068719CA00001), the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (DHHS: grant number IDSEP190051-01-0200). Finding for sequencing: Bill & Melinda Gates Foundation (GCE/ID OPP1211841), Chan Zuckerberg Biohub, and the Innovative Genomics Institute at UC Berkeley. 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). HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928-04, 5K24AI131924-04), Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (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 (NEPADAgency) with funding from the Wellcome Trust [grant #107752/Z/15/Z] and the United Kingdom (UK) government. 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”. Darren P. Martin is funded by the Wellcome Trust (Wellcome Trust grant number 222574/Z/21/Z). Cathrine Scheepers at the NICD is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under the Award Number U01AI136677. Furthermore, pandemic surveillance in South Africa and Senegal was supported in part through National Institutes of Health USA grant U01 AI151698 for the United World Antiviral Research Network (UWARN). Support for pandemic surveillance from Prof. Tulio de Oliveira group to other African countries is funded by the Rockefeller Foundation. Sequencing efforts in the Democratic Republic of the Congo were funded by the Bill & Melinda Gates Foundation under grant INV-018030 awarded to CBP 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 National Institute of Health Research (NIHR) Global Health Research program (16/136/33) using UK aid from the UK government (funding to EM and NR 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. Samples collection and typing in Mali were supported by Fondation Merieux-France and Sequence efforts has been supported by the 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 were supported by grants from the National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov), NIH-H3Africa (https://h3africa.org) (U01HG007480 and U54HG007480), the World Bank grant (worldbank.org) (ACE IMPACT project) to Christian Happi. Author contributions: Conceptualization: EW, HT†, JGS, JO, JOG, KOD, RAD, RAK, RL, SKT, SM±, TdO. Methodology: ANZ, AR, CA, DPM, DR, EW, HT†, JAE, JG†, JGS, KHY, KOD, LdOM, MAB, MC, MG, MMN, MVTP, PA, TdO, VF. Investigation: AE, AI†, ANZ, AR, AS†, AvG, CAK, CW, DC, DN, DPM, DR, DS, EM, EN, EW, FL, GG, HT†, JAE, JES, JG†, JGS, JJT, JL, JN‡, JQM, KHY, M-MD, MAB, MC, MG, MM†, MM±, MS, MVTP, NA, NHR, NK, PK, RAAC, RAD, RG, SAM, SFA, SM±, SO, TLV, VF, WP. Sampling: A-SK, AA, AAA, AAS, AD, AE, AEOO, AF, AG, AH, AI, AK†, AKS, AKS†, AL, AMO, AO, AP, AR†, AS‡, AV, AVG, AvG, BB, BH, BK, BK†, BM, BN, BO, BT, CA, CD, CP, CS, CW, DB, DC, DD, DG, DGA, DN, DS, EKL, EM, EMO, EN, EP, ES, FA, FA‡, FE, FM, FM†, FO, FT, FT†, GAA, GG, GM, GPM, GT, GvZ, HC, HE, HN, IC, IG, IG†, IK, IM, IO, IS, JA, JCM, JD, JES, JG, JG†, JJL, JK, JL, JMH, JMM, JN, JN†, JTK, KA, KMS, LB, M-MD, MA†, MC, MD, MeH, MGS, MKK, MM§, MM†, MM±, MMD, MN, MO†, MOA, MR, MS, MWM, MY, NA, NG, NH, NHR, NI, NK, NM, NN, NS, NS†, OC†, OEC, OF, OF†, OI, OJ, OK, OO, OP, OS, OT†, P, PB, PC, PCS, PD, PK, PKQ, PO, PS, RAD, RG, RN, SA, SA†, SB, SBL, SD, SE, SeK, SFA, SG†, SK, SL, SLD, SM, SM†, SMM, SN, SP†, SS, ST, TLV, TM, TS, UC, UG, UJ, UR, VG, WA, WC, WP, WR, YB, YKT, YN, ZRD. Sequencing: A-SK, AA, AAA, AAS, AC, AD, AEOO, AF, AI, AI‡, AK, AK†, AKK, AKS, AKS†, AL, ANZ, AP, AS, AS†, AS‡, ASO, AT, AV, AVG, AvG, AY, BB, BD, BH, BK, BK†, BM†, BN, BT, CA, CB, CBP, CD, CMM, CP, CS, DB, DD, DG, DGA, DJB, DLB, DM, DOO, DP, DSYA, DT, EF, EFN, EKL, EL, EMO, EP, ES, ES†, ESL, FA, FA†, FAD, FD, FM, FM†, FO, FT†, FW, GAA, GG, GPM, GT, GvZ, HA, HA†, HC, HCR, HE, HG†, HK, HN, IB, IC, IG, IG†, IK, IM, IS, JA, JB, JCM, JD, JF, JG, JG†, JJL, JK, JMH, JMM, JMN, JN, JN†, JQM, JTK, JY, KA, KMS, KOD, KS, KT, LB, LF, LS, LT, M-MD, MA†, MAB, MC, MD, MeH, MGS, MIM, MKK, MM, MM§, MM‡, MMD, MMN, MO, MO†, MOA, MVTP, MWM, MY, ND, NG, NH, NI, NI†, NM, NN, NN†, NS, NS†, NT, OC, OC†, OEC, OF, OI, OJ, OT†, PA, PB, PCS, PD, PEO, PK, PKQ, PM, PO, PS, RAAC, RG, RN, ROP, SA, SA†, SB, SBL, SCS, SD, SE, SE, SeK, SG, SG†, SHA, SK†, SL, SLD, SM, SM†, SM±, SMM, SN, SP†, SP‡, SR, SS, ST, ST†, SvdW, TA, TM, TM†, TS, UC, UG, UJ, UJA, UR, VG, WA, WC, WR, YB, YB†, YKT, YN, ZRD. Visualization: AC, AI‡, AK, AKK, AS, AS†, AY, BT, CB, CMM, DB†, DOO, DP, DR, DSYA, EA, EB, ESL, EW, FAD, FB, FD, FW, GS, HA, HA†, HG†, HL, HT†, IA, IS, JAE, JB, JF, JG†, JMN, JY, KHY, KS, LF, LS, LT, MA, MA†, MG, MT, MVTP, MW, ND, NI†, NK, NN†, NT, OC, OT, PA, PCS, PEO, RAAC, SB, SFS, SHA, SK†, SM±, TA, TM†, VE, YB†. Funding acquisition: AJP, AR, AvG, BK, CA, CAK, CBP, CW, DC, DJB, DN, FL, GAA, GG, GPM, HC, JES, JJT, JL, JMH, JN‡, JO, KOD, M-MD, MC, MIM, MM±, MVTP, NA, PCS, PK, PM, RAK, SAM, SE, SM†, SvdW, TdO, WP. Project administration: AJP, AR, AV†, AvG, BK, CW, DJB, DN, EW, FA†, FT, GAA, GPM, GS, GT, HC, JCO, JJT, JMH, JO, JOG, JY, KOD, MC, MK, MM†, MP, MVTP, MW, NR, OT, PCS, PK, PM, RAK, SAM, SE, SFS, SG†, SM†, TdO. Supervision: AJP, AR, BK, CW, DN, EN, EW, FT, GAA, GK, HC, JB, JMH, JN‡, JO, JOG, KOD, MA†, MC, MIM, MM†, MMN, MS, NM†, NR, PCS, PK, PM, RAK, SE, SeK, SG†, SM, SM†, SP, TdO. Writing – original draft: AKS, ANZ, BK, DPM, EW, FT, GK, HT†, JB, JCM, MA†, MAB, MC, MG, MM, NM†, RL. Writing – review and editing: ANZ, BK, CMM, DN, DPM, DR, DSYA, DT, EKL, EL, ESL, EW, HT†, JES, JGS, LdOM, MAB, MC, MeH, PKQ, PM, RL, SKT, TdO, UJA. *Author’s contributions listed alphabetically. A full list of author abbreviations is included on the GitHub deposit (https://github.com/krisp-kwazulu-natal/africa-covid19-genomics) (23). Competing interests: Dr. Pardis Sabeti is a founder and shareholder of Sherlock biosciences, and is both on the Board and serves as shareholder of the Danaher Corporation. The authors declare no other conflicts of interest. Data and materials availability: All sequences that were used in the present study are listed in table S4 (accessible on the GitHub repository) along with their GISAID sequence IDs, dates of sampling, the originating and submitting laboratories and main authors. All input files (e.g., alignments or XML files), all resulting output files and scripts used in the study are shared publicly on GitHub (https://github.com/krisp-kwazulu-natal/africa-covid19-genomics) (23). This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party, obtain authorization from the rights holder before using such material.