The aim of this study was to determine the dependence of the total phenolic, flavonoid, and extractive content in extracts of Origanum vulgare L. on the soil pH, humus, total nitrogen (Ntotal), and plant-available/mobile phosphorus (P2O5), as well as potassium (K2O), total calcium (Ca), magnesium (Mg), and sodium (Na) concentrations. Experimental fields were formed in four locations in Lithuania. Soil and perennial O. vulgare samples were taken at three sites of each experimental field. A total of 12 samples of soil and 12 samples of the tested plant were collected and analyzed. The concentrations of bioactive compounds in plants are significantly (p < 0.05–0.01) affected by some chemical properties of the soil: the total phenolic content was reliably correlated with the soil pH, Ntotal, Ca, Mg, and P2O5; the flavonoid content was correlated with the soil P2O5, K2O, Mg, and Na; and the extractive content was correlated with the soil humus, Ntotal, and Na. The obtained results are useful for the development of the commercial cultivation of O. vulgare.