Maize is a staple crop important for food security that millions globally depend upon as an energy source, primarily due to its high starch and fat content. For growth and disease resistance, maize production requires a balanced intake of essential nutrients, including nitrogen (N), phosphorus (P) and potassium (K). This study investigated the relationship between soil nutrient levels and maize disease occurrences in the Mopani District Municipality, Limpopo Province, South Africa. Soil and maize leaves were collected using a systematic sampling approach. Grids of 10 × 10 m were created, covering a maize field. Forty soil samples were collected a day before the planting date and sent to the laboratory for analysis of N, P and K. During the tasseling stage of the maize plant, 40 maize leaf samples were collected and sent to the laboratory for disease identification. Maize leaves were classified as healthy, southern corn leaf blight (Bipolaris maydis), northern corn leaf blight (Exserohilum turcicum), maize streak disease (Maize streak virus), nitrogen-deficient or phosphorus-deficient. Generalized Linear Models (GLMs) with a corrected Akaike Information Criterion (AICc) showed a significant relationship between low soil nutrient levels of N, P and K and maize disease occurrence (p < 0.0001). The interaction of the N*P*K model had the lowest AIC value (AICc = 28.53), indicating the necessity of considering synergistic effects in maize disease management. All the model performances had a delta AICc = 0. These findings highlight the significance of comprehensive soil management strategies in enhancing the disease resistance, well-being and yields of maize crops.