Micronutrient malnutrition is a global challenge. However, there are promising opportunities for combating it through the consumption of neglected and underutilized leafy green vegetables. Senecio biafrae is an underutilized and nutrient-rich green leafy vegetable with huge nutritional and health potentials that have remained unexploited. The aim of this research was to evaluate the proximate, mineral, vitamin, anti-nutrient contents of the leaves of Senecio biafrae. Leaves of Senecio biafrae were collected from five communities in Ekiti State and analyzed using standard biochemical methodologies. The results showed that the leaves differed significantly in nutritional and anti-nutritional contents. The leaves were rich in potassium, magnesium, and calcium, and low in fat and anti-nutrient contents for all the groups studied. The Pearson’s correlation results showed that most of the nutritional parameters either had inverse or no relationships with anti-nutrients. The crude protein showed significantly positive correlations with dry matter (0.90**) and a negative correlation with cyanogenic glycosides (-0.90**). Cyanogenic glycosides showed significantly negative correlations with potassium (-0.63**), calcium (-0.66**) and dry matter (-0.44*). Nitrate showed no significant relationship with any nutritional parameter. Oxalate and tannin showed no significant relationship with the vitamins. Phytate and tannin showed no significant relationship with the proximate contents and minerals. The results showed that Senecio biafrae leaf is nutrient-rich and could help to mitigate the effects of micronutrient deficiencies. The variations and relationships among the nutritional and anti-nutritional parameters could enhance meaningful selection and nutritional quality through breeding.