The aim of the study was to demonstrate the effect of the cultivation system, cultivars and pre-sprouting of potato on soil quality. Materials for the research were obtained from a three-year (2016–2018) field experiment in Central-Eastern Poland. The experiment was established using the randomized sub-blocks method, in a dependent system which was as follows: split-split-plot in three replications. The first order factor was the type of cultivation system of organic (E), and sustainable (S). The second order factor was the selection of the six potato cultivars (‘Denar’, ‘Gwiazda’, ‘Jurek’, ‘Satina’, ‘Tajfun’, ‘Jelly’) and the third order factor was the pre-planting treatments of (A) sprouted seed potatoes, and (B) non-sprouted seed potatoes. The organic cultivation system, in comparison to the sustainable system, contributed to changes in the chemical properties of the soil by increasing the content of organic C and total N, thereby narrowing the C:N ratio, reducing the content of mineral N forms, changing soil acidity, and changing in the enzymatic activity of Adh, AFs, and APs in the soil. Germination of seed-potatoes contributed to the increase in total N and nitrate N in the soil, to extend the C:N ratio. The sustainable development of agriculture in the soil and climate conditions of Central-Eastern Poland can be achieved by maintaining soil fertility and improving its productivity, and reducing the risk of the agricultural system by increasing the flexibility of integrated agriculture.