A field experiment aimed to evaluate grain yield and grain quality of winter wheat cultivated in a 35-year cereal monoculture and three soil tillage systems (TSs). Winter wheat grown in the plot after common pea (PS) served as the control. In the monoculture (MON) and on PS plots, winter wheat was sown in the conventional (CT), reduced (RT), and no-tillage (NT) systems. In the CT system, shallow plowing was applied after the previous crop harvest, followed by pre-sow plowing. In the RT system, a cultivator was used, and the pre-sow plowing was replaced with a pre-sowing set. In turn, in the NT system, the soil was treated with glyphosate and cultivated using a pre-sowing cultivation set. Winter wheat produced over 2-fold higher grain yield on the PS plot than in the MON as well as in the CT than in the RT and NT systems. In turn, the plant number after emergence was differentiated only by the cropping system (CS). On the PS plots, the number of plants after emergence was 15.6% higher, and the spike number was 50.5% higher than on the MON plots. Also, more spikes per m2 were found on the CT than on the RT and NT plots. Similarly, the grain weight per spike and the 1000 grain weight were higher on the PS plots compared to the MON plots as well as in the CT than in the RT and NT systems. The evaluation of the variance analysis components shows that the grain yield, plant number after emergence, spike number, grain number per spike, and 1000 grain weight were more strongly influenced by CS than by TS. Grain quality, expressed by the contents of total protein, wet gluten, and starch, as well as by Zeleny’s sedimentation index and grain uniformity index, were affected to a greater extent by CS than TS and reached higher values in the grain harvested from the PS plot compared to MON.