Public Health Genomics (PHG) is a relatively new field. The wide application of genomic technologies played a pivotal role in elucidating the full genomic sequence of the SARS-CoV-2 virus. This breakthrough proved to be the starting point in the manufacture of diagnostic kits and the subsequent making of vaccines. Beyond the COVID-19 pandemic, many African countries can take advantage of the various investments in genomic technologies to introduce and intensify the use of genomics for public health gain. Public Health Genomics effectively monitors, prevents, and manages non-communicable and infectious diseases. However, there are several challenges to implementing PHG in Africa. In this perspective article, we discuss the utilization of PHG during the COVID-19 pandemic, the lessons learned from using PHG to manage and contain the COVID-19 pandemic, as well as potential challenges Africa may face when putting PHG into practice compared to challenges of other regions. We also discuss our recommendations for overcoming these challenges.