This study aimed at assessing the knowledge about healthcare risk waste (HCRW) management among doctors, professional nurses, pharmacists and laboratory technicians, in accordance with National Environmental Management, Waste Act 59 of 2008, Constitution of South Africa and sustainable development goals (SDG). The quantitative cross-sectional study was conducted, using self-administered questionnaires and stratified random sampling was used. Data was analyzed using the descriptive and inferential statistics. One hundred and forty-four participants were included in the study. The majority 90.28% of the participants were aged 19–50 years, females (71%), professional nurses (36%), and they had 1–10 years of experience (71%). The health professionals were knowledgeable of sharps waste (89%), slightly over (52%) knew anatomical waste, whereas (27%) and (17%) knew radioactive and cytotoxic waste, respectively. Health professionals (92%) agreed that the sharps-waste container should be disposed of in a yellow bin container, at least (63%) and (27%) agreed that red liner and box should be used for both infectious non anatomical waste and for cytotoxic waste. The null hypothesis was tested on knowledge versus age, profession and gender, and evidence against it was found on waste storage period in all three variables where chi-square and Fisher exact p-values were less than the 5% significant level. More attention should be directed towards similar HCRW management training at the hospital for all health professionals and behavior modification. The hospital management must ensure that HCRW-trained health professionals and HCRW management officials put into practice what they have learnt.