Considering the global tendency towards using valuable secondary metabolites of plant origin, there is a need to optimize the cultivation of herbal plants, e.g., the meadow arnica (A. chamissonis Less.). The inflorescences of this species (Arnicae anthodium) have a similar chemical composition and pharmacological activity to that in the mountain arnica (Arnica montana L.), and can be cultivated more easily than the mountain arnica. Therefore this study assesses soil and fertilization effects on the flower head yield and concentrations of active substances (sesquiterpene lactones, flavonoids, and essential oil) with great importance for application in the pharmaceutical and cosmetic industries. A field experiment was carried out during 2017–2019 on two types of soil (sandy and loamy soils) differing in the pH values, organic matter content, and the P, K, and Mg levels. Five levels of nitrogen fertilization were applied in both soil variants: 0, 30, 60, 90, and 120 kg N∙ha−1. The study showed that both the soil type and the nitrogen fertilization had a positive impact on the raw material yield and the content and yield of the main active substances. The cultivation of arnica in the loamy soil was more favorable—it provided a higher flower head yield, higher levels of sesquiterpene lactones, flavonoids, and essential oils, and consequently, a higher yield of these metabolites. High flower head yields were achieved at doses of 60 and 90 kg N∙ha−1. The content of sesquiterpene lactones and essential oils increased in the consecutive study years along with the increase in nitrogen doses. The highest content of flavonoids was detected in flower heads obtained from three-year-old plants fertilized with 60 kg N∙ha−1. High yields of sesquiterpene lactones and essential oils were obtained at doses of 90–120 kg N∙ha−1, whereas the fertilization with 60–90 N∙ha−1 ensured a high yield of flavonoids. The yields of sesquiterpene lactones and essential oil did not depend on their concentration but correlated with the increase in the yield of flower heads of plants cultivated in both sandy and loamy soil variants. In turn, the yield of flavonoids was influenced by both their concentration and the flower head yield. The flower head yield, the content of sesquiterpene lactones, flavonoids, and essential oils, and the yields of metabolites presented in this study indicate favorable climatic conditions for the cultivation of A. chamissonis in Central and Eastern Poland. This proves that a wide range of pharmacologically active substances can be produced in this region of Europe.