The present invention provides a compound fertilizer, which comprises an organic-inorganic compound fertilizer and a compound microbial fertilizer. The invention also provides a preparation method of the compound fertilizer and a fertilization method for flue-cured tobaccos. According to the technical scheme of the invention, a large number of nitrogen, phosphorus and potassium element nutrients and medium trace element nutrients are mixed with organic materials, and an obtained mixture is subjected to fermentation or granulation to prepare the compound microbial fertilizer or the organic-inorganic compound fertilizer. The compound microbial fertilizer and the organic-inorganic compound fertilizer are applied into the soil together. In this way, not only the chemical or physical fixation rate of inorganic nutrients in the fertilizer by the soil and the loss amount of the inorganic nutrients are reduced, but also the release of the inorganic nutrients in the fertilizer slows down. Meanwhile, the effectiveness of the inorganic nutrients is improved and the utilization rate of the fertilizer is increased by more than 15%. The application amount of the chemical fertilizer is reduced by more than 5%.