Black shank disease is an important factor limiting the yield of flue-cured tobacco. Soil amendments have the potential to improve soil health and increase crop yield and quality. However, the application effects of soil amendments have not been elucidated in flue-cured tobacco. Here, we conducted field experiments in the major tobacco planting area, Exploring the effects of plant stem cell soil amendments at different levels on the occurrence and physiological growth of tobacco black shank disease, The purpose is to evaluate the effectiveness of plant stem cell soil amendments and recommend feasible applied rates. Plant stem cell soil amendments are applied at four levels: T0 (0 kg ha−1), T1 (1500 kg ha−1), T2 (2250 kg ha−1), and T3 (3000 kg ha−1). Nutrient absorption, agronomic traits, dry matter quality, chemical composition, and economic benefits of flue-cured tobacco black shank disease were explored. The results showed that the application of plant stem cell soil amendments effectively reduced the incidence rate of tobacco black shank disease, and significantly improved the agronomic traits (leaf number, plant height, leaf length, and width) and dry matter quality of flue-cured tobacco. At the same time, the nutrient content (N, P, and K), the proportion of high-quality tobacco leaves, and the content of coordinated chemical components (total nitrogen, total plant alkali, total sugar, reducing sugar, potassium and chlorine) of flue-cured tobacco plants were increased. In addition, the application rate of stem cell soil amendment at 3000 kg ha−1 showed the best effect on reducing the occurrence of black shank disease, which resulted in improved tobacco yields and economic benefits to the greatest extent of flue-cured tobacco. The study indicates that plant stem cell soil amendments can significantly enhance the yield and quality of flue-cured tobacco and offers an effective method for sustainable crop production in the tobacco industry.