Inorganic fertilizer application and the quantity required by the crop for optimum production led agronomists to introduced varying measures in crop production. A study to investigate the effects of single and split NPK 15-15-15 fertilizer application on muskmelon (Cucumis melo L.) production was conducted at the Teaching and Research Farm of Ekiti State University. A 4 × 2 factorial experiment laid out in a Randomized Complete Block Design in three replicates with four varying rates (0, 167, 333 and 500 kg ha-1) of NPK 15-15-15 fertilizer applications and two-mode of applications (single and split) serves as the treatments. Data collected include the number of leaves and branches, vine length, number of fruits, fruit length and width, fruit weight, fruit flesh thickness (fruit pulp width), number of seeds fruit-1 and seed weight. Collected data were subjected to analysis of variance (ANOVA), and treatment means separated with Duncan Multiple Range Test at 5% level of probability. The split application at 333 kg ha-1 NPK fertilizer produced a significantly higher number of leaves (90), leaf area (109.58 cm2) and vine length (110.77 cm) at 10 WAS than other applied fertilizer rates. The split application of 500 kg ha-1 NPK fertilizer produced a higher fruit yield (12.64 t ha-1) than 12.09 t ha-1 from the single application which was not significantly different from the 333 kg ha-1 NPK fertilizer. The results indicated that the split application of NPK fertilizer is a better fertilizer application approach than a single application for muskmelon production.