Climate change is a global problem, which affects the various geographical regions at different levels. It is also associated with a wide range of human health problems, which pose a burden to health systems, especially in regions such as Africa. Indeed, across the African continent public health systems are under severe pressure, partly due to their fragile socioeconomic conditions. This paper reports on a cross-sectional study in six African countries (Ghana, Nigeria, South Africa, Namibia, Ethiopia, and Kenya) aimed at assessing their vulnerabilities to climate change, focusing on its impacts on human health. The study evaluated the levels of information, knowledge, and perceptions of public health professionals. It also examined the health systems’ preparedness to cope with these health hazards, the available resources, and those needed to build resilience to the country’s vulnerable population, as perceived by health professionals. The results revealed that 63.1% of the total respondents reported that climate change had been extensively experienced in the past years, while 32% claimed that the sampled countries had experienced them to some extent. Nigerian respondents recorded the highest levels (67.7%), followed by Kenya with 66.6%. South Africa had the lowest level of impact as perceived by the respondents (50.0%) when compared with the other sampled countries. All respondents from Ghana and Namibia reported that health problems caused by climate change are common in the two countries. As perceived by the health professionals, the inadequate resources reiterate the need for infrastructural resources, medical equipment, emergency response resources, and technical support. The study’s recommendations include the need to improve current policies at all levels (i.e., national, regional, and local) on climate change and public health and to strengthen health professionals’ skills. Improving the basic knowledge of health institutions to better respond to a changing climate is also recommended. The study provides valuable insights which may be helpful to other nations in Sub-Saharan Africa.