The present study was carried out to examine the combined effects of varying seed sowing and multinutrient fertilizer levels on maize yield in Shire area, Northern Ethiopia, in two consecutive cropping seasons (2018-2019). The experimental plots were designed in a split plot design with three replications. Sowing dates were determined based on the rainfall criteria of the AquaCrop model. Accordingly, the sowing date treatments were set as June 1, June 7, June 12, and June 16 for the 2018 cropping season, and the corresponding sowing dates for the 2019 cropping season were May 26, June 3, June 8, and June 12. The multinutrient fertilizer levels included 0, 100, 200, and 300 kg·ha−1. Agronomic related data were subjected to the analysis of variance, and partial budget analysis was applied for the economic performance evaluation. Maize yield was agronomically and economically influenced by sowing dates and multinutrient levels. Relative yield superiority that varies between 48.9 and 87.7% was found for each 100 kg·ha−1 multinutrient applied. On the other hand, with 4–6 days shifted towards earlier sowing resulted in an average yield increase by 4.9–66.9%. Application of 300 kg·ha−1 multinutrient for the early sown maize seems agronomically the superior treatment. However, from the economic analysis perspective, early maize sowing combined with the application of 200 kg·ha−1 multinutrient fertilizer was reported as the most profitable treatment. Late sowing of maize with the application of multinutrient fertilizer beyond 200 kg·ha−1 resulted in negative economic returns. The regression analysis results also indicated that maize grain yield tends to increase with the level of multinutrient fertilizer application (R2 = 0.841–0.864), whereas yield decreased with the delay in sowing dates (R2 = 0.927–0.995). Hence, this study concluded that the treatments with the best agronomic performance are not necessarily the best in terms of profitability.