This paper reviews and analyses the importance of maize as staple food in Eastern and Southern Africa (E&SA) and contributes in understanding the nexus between maize nutritional composition and prevalence of micronutrient deficiencies (MNDs) in these regions. MNDs remain a major public health concern particularly for women and children, with calcium, iodine, iron, selenium, zinc, folate and vitamin A deficiencies being the most common. Estimates of their prevalence are among the highest in E&SA: iron-deficient anemia affected 26 to 31% of women of reproductive age, and deficiencies up to 53%, 36%, 66%, 75% and 62% for vitamin A, iodine, zinc, calcium and selenium, respectively, were measured in populations of these regions. Besides, these two regions show the highest worldwide maize per capita consumption (g/person/day) as main staple, with 157 in Eastern Africa and 267 in Southern Africa, including up to 444 in Lesotho. The analysis of food composition tables from these regions showed that 100 g of maize foods consumed by these populations could to some extent, contribute in satisfying dietary reference intakes (DRIs) of children and women in energy, proteins, carbohydrates, magnesium, zinc, vitamins B1 and B6. However, it provides very low supply of fats, calcium, sodium, selenium, vitamins C, A and E. The high occurrence of MNDs and considerable nutritional potential of maize consumed in E&SA can be explained by loss of nutrients due to processing practices, low food diversification and reduced nutrients bioavailability. Success cases of the main strategies to tackle the issue of MNDs in these regions by improving maize nutritional quality are discussed in this paper. Maize fortification was shown to improve nutrition and health outcomes of population. Increasing dietary diversity by complementing maize with other foods has improved nutrition through integration of micronutrient-rich foods in the diet. Mostly, biofortification has successfully contributed in reducing vitamin A and zinc deficiencies in rural communities more than nutrient supplementation, fortification and dietary diversity.