To improve the comprehensive utilization of planting and breeding waste resources, corn straw and cow manure were used as raw materials for exploring the molding process parameters for preparing agricultural fertilizers via compression after mixing. The pressure, compression speed, and holding time were the experimental factors, while the block drainage, compression ratio, and dimensional stability were used as evaluation indicators. This study analyzed the influence of various factors on the quality evaluation index of the formed blocks. The results show that the best factor ranges were as follows: a pressure of 15 kN to 24 kN, a compression speed of 200 mm/min to 400 mm/min, and a holding time of 30 s to 60 s. A ternary quadratic regression and rotating-combination test design was used to optimize the combination of forming parameters as well as performing test verification. The formed block yielded the following results: a block drainage of 6.29%, a compression ratio of 3.37, a dimensional stability of 86.5%, a pressure of 23.9 kN, a compression speed of 276 mm/min, and a holding time of 53.1 s. These results can provide a reference for the molding process and equipment development of corn straw and cow manure mixed fertilizer.