In Ohio, changes in nitrogen (N) fertilizer application rates and row spacing in combination with fungicide applications have been proposed as possible strategies for increasing wheat productivity and profitability. Field experiments were conducted in 2013, 2014, and 2015 to evaluate the benefits of increasing row spacing and N rates in soft red winter wheat as influenced by diseases. Combinations of narrow (19 cm) and wide (38 cm) row spacings, N rates ranging from 34 to 180 kg ha-1, and the fungicide prothioconazole + tebuconazole applied at flag leaf emergence, boot, or early anthesis represented different management programs. Linear mixed model analyses were performed to evaluate the effects of N, row spacing, and fungicide timing on leaf rust, Fusarium head blight (FHB), and deoxynivalenol (DON), and to quantify relationships among leaf rust, N, grain yield (YLD), and test weight (TW). YLD, TW, grain prices and price discounts, as well as input costs were used to estimate net cash income (NCI) for each management program. Wide row wheat had statistically higher mean FHB and DON, and lower mean yield and test weight than narrow row wheat in 2014 and 2015 but not in 2013. There were significant positive linear relationships between leaf rust and N as well as YLD and TW with N. Differences in FHB and DON among N rates were not statistically significant. Leaf rust severity was consistently lower in treated plots, with efficacy influenced by N rate and application timing. Programs with narrow row spacing and treated with the fungicide generally resulted in the highest mean YLD and TW across N rates. Price discounts due to high FDK and DON, and low TW were higher, and consequently, NCIs were lower in 2014 and 2015 than in 2013. The highest NCIs were obtained for programs with the highest YLD and lowest price discounts, consequently programs with wide row spacing, a fungicide treatment, and high N rates were only economically beneficial when FHB levels were low and grain prices were high.