In order to identify the impact of nitrogen and sulfur fertilizer on the yield and grain quality of spring wheat as well as on the improvement of its chemical and health-promoting properties, a strict 3-year field experiment was carried out. The subject of the experiment was the Kandela variety of spring wheat (Triticum aestivum L.) fertilized with various rates of nitrogen (factor I) and sulfur (factor II). The experiment was carried out in the years 2014–2016 in a split-plot design, in a private farm in Malice near Hrubieszów (Poland), on dystrophic typical medium brown soil, made of medium-grained sandy loam and classified as a good rye soil complex. The experiment included 2 factors (in four replicates): I. nitrogen fertilization at a rate of 0, 50, 100, and 150 kg ha–1; II. sulfur fertilization at a rate of 0 and 40 kg ha–1. After harvesting spring wheat, grain yield (at 11% moisture content) from each plot was determined (kg) and converted into t ha–1. The following grain quality characteristics were examined in the dry matter: starch content (g kg–1), gluten content (g kg–1), total protein (g kg–1), cysteine (mg g–1), methionine (mg g–1), fat (g kg–1), and crude fiber (g kg–1). As regards the features influencing health-promoting properties, the content of flavonoids (expressed as quercetin equivalents; %) and o-dihydroxy phenols (expressed as caffeic acid equivalents; %) was determined. Based on the conducted research, it was shown that the application of nitrogen (factor I) at the rates of 100 and 150 kg ha–1 and sulfur fertilization (factor II) at a rate of 40 had the most beneficial effect (statistically significant difference) on spring wheat grain yield. The use of a rate of 50 kg N ha–1, regardless of sulfur addition, was insufficient because it did not produce beneficial effects. It should be stated that under negative sulfur balance in the cultivated soils of the study area, it is necessary to use sulfur fertilizers. To sum up, the obtained research results indicate that in the spring wheat production system, the variant of 150 kg N ha–1 combined with 40 kg S ha–1 should be recommended. This variant of fertilization had a significant positive impact on both the productivity and the qualitative and health-promoting characteristics of spring wheat grains.