Mushroom cultivation is a source of organic, sustainable food that is growing rapidly to become a profitable sector of agriculture. Nutritional supplements and natural medicines are provided by many mushroom products, including the Agaricus blazei Murrill mushroom. In recent years, the classical culture system has begun to be used more in less-developed countries, providing an additional gain for locals. The content of the article is based on the deductive research method, starting from theory to practice. This paper aimed at the economic efficiency of the Agaricus blazei Murrill mushroom crop using four substrate recipes and two protein additives, following the economic efficiency of the crops and the composition of production costs for the classic semi-mechanized production system. According to prepared technological sheets, the principal component analysis of the main economic indicators highlighted the experimental variant V5 (Synthetic substrate, with 3% wheat bran protein addition) with the highest labor productivity, obtaining 6.48 kg md−1, the equivalent of 194.3 RON md−1, and a profit rate of 80.42% compared to the V10 variant (reed substrate without protein addition), where the profit rate was only 26.16%. The addition of 3% wheat bran protein to the synthetic culture substrate (V5) brings an increase in global production with 45 RON sqm−1 compared to the variant without protein addition (V4). The research carried out is of practical use, especially for small producers using classical mushroom cultivation technology, and can be extended to other harvested mushroom species.