The coronavirus disease 2019 (COVID-19) pandemic is a global public health problem that has affected the globe in different ways. There is little information published on the challenges and lessons learnt in responding to the COVID-19 epidemic in Zambia. Objective: To establish Zambia's response, lessons and the challenges experienced in the fight against COVID-19. Results: Since the emergence of COVID-19, Zambia has experienced three waves, with the third wave being the most severe. The Zambian government responded positively and effectively to all three pandemics with the help of cooperating partners. Zambia adopted the World Health Organization (WHO) recommended prevention methods such as hand hygiene, masking up in public, physical distancing, avoiding crowded areas and staying at home to prevent the further spread of the disease. Additionally, surveillance of COVID-19 was strengthened, which led to the early detection of cases. Besides, there has been a strong call for all Zambian adults to receive the COVID-19 vaccine as a way of controlling the epidemic. However, since the launch of the COVID-19 vaccination programs, there has been a high level of vaccine hesitancy, causing Zambia to fall below the 10% of the adult population required to be vaccinated. Conclusion: The Zambian government put in place effective strategies in the fight against COVID-19. However, a lack of resources, misinformation, myths and vaccine hesitancy posed challenges in the fight against COVID-19 in Zambia. There is a need for continuous public education and sensitization on COVID-19