Post-harvest losses contribute significantly to food insecurity and affect the nutritional status and health of populations. This study estimates the waste of fresh fruits in the post-harvest chain and identifies avoidable causes along the food supply chain to extrapolate good practices for the empowerment of retailers. A semi-structured questionnaire and a checklist were used in the administrative units of Yaoundé, Cameroon, from May to June 2017. Fifty fresh fruit retailers were randomly selected. Information, including socioeconomic profile, handling practices, transport, and food wastes, was analyzed. Dominant figure in the fruit market are 34-aged women. Despite significant professional experience, none of retailers received formal training. The perceived main causes of fruit waste were failure to sell, mechanical damage during transport, and storage conditions. Inappropriate packaging materials and poor hygiene were also observed, and about 40–50% of fruits did not reach the consumers’ table. Nutritional education of the general population is crucial in facing the challenge of fresh fruit waste. The analysis of critical points in the post-harvest fresh fruit chain highlights good cost-effective practices. Training and empowerment of retailers represent the main measures to decrease fruit waste, in addition to nutritional training programs for the general population recommending the daily consumption of fruits for healthy life.