The milk thistle is a highly valuable medicinal plant, widely used in treatment of liver diseases. Soil-climate conditions of the steppe zone of Ukraine are favourable for crop cultivation. The goal of the study was to determine relations between milk thistle productivity and elements of cultivation technology, viz., primary tillage depth (14–16 and 20–22 cm), inter-row spacing (30, 45, 60 cm), timing of sowing (3rd decade of March, middle of April, 3rd decade of April) and mineral fertilizer application doses (no fertilizers, N45P45, N90P90). Field trials were carried out during the period from 2010 to 2012 on the irrigated lands of the Institute of Rice of the National Academy of Agrarian Sciences of Ukraine by using the split plot design method in four replications. The climate of the territory of the trials is typical for the steppe zone. The soil type was dark-chestnut residual solonetz middle-loamy soil. We used the Yuhoslava variety of milk thistle in the trials. Cultivation technology was standard, excluding the studied factors. The results of the trials showed significant impact of all the studied cultivation technology elements on milk thistle seed and oil yields. The maximum average seed (1.66 t/ha) and oil (489 kg/ha) yields were obtained under the primary tillage at the depth of 20–22 cm, inter-row spacing of 60 cm, sowing in the 3rd decade of March, applying mineral fertilizers in a dose of N90P90. The highest input in seed and oil yields rise was made by the mineral fertilizers, which increased milk thistle productivity by 1.57 times comparatively with non-fertilized treatments. We also established a strong direct interrelationship between seed and oil yield: coefficient of determination was 0.96. Results of the current study are slightly limited, so further investigations in the field of milk thistle cultivation technology development and improvement are required to provide Ukrainian farmers with scientifically grounded agrotechnology of this valuable medicinal plant.