Wheat-maize double cropping system is the main cropping system in North China Plain. The aims of the present study were to delineate the responses of soil microbial biomass N (SMBN), soil microbial biomass C (SMBC) and enzymes activities to different fertilization methods of maize and limited irrigation treatments of wheat. The split plot experiment design was adopted on the field experiment. The main control was fertilization methods of maize, F1 (conventional method, 5cm depth of subsoil with sowing) and F2 (application N, P, K fertilizers to designated different soil depth with subsoiling), and the sub-control was three irrigation treatments in the growing season of wheat, W0 (no irrigation events after the overwintering stage), W1 (irrigation at the jointing stage after overwintering), and W2 (irrigation at jointing and flowering stages after overwintering). The results showed that: (1) Subsoiling fertilization in maize season was beneficial to increase the supply of N, P and K, improve soil fertility, and significantly affected the physical and chemical properties of topsoil in wheat flowering stage. In 0—20 cm and 20—40 cm soil layers, soil moisture content and nitrate nitrogen content of F2W2 treatment were significantly higher than those of other treatments. Soil water content was affected by F2 and limited irrigation of wheat, and the interaction effect was significant (p＜0.05). The effect of water treatment on nitrate nitrogen was significantly greater than that of subsoil fertilization. (2) SMBC and SMBN were not only affected by fertilization of F2, but also limited irrigation of wheat. Irrigation in wheat growing season significantly increased the contents of SMBC and SMBN in 0-20 cm soil layer, and soil water content had a significant effect, contributing 78.3%. In 20—40 cm soil layer, the content of SMBC and SMBN were significantly affected by fertilization methods in maize season and limited irrigation treatment in wheat season, and their interaction had significant effects on the content of SMBN. The soil water content had significantly effect on the SMBN, contributing 88.9%. The SMBN content of 0—20 cm under F2W2 was 94.16 mg/kg, which was significantly higher than that of other treatments(p＜0.05). The SMBN and SMBC contents of 20—40 cm under F2W2 were 57.57 mg/kg and 243.77 mg/kg, respectively, which were significantly higher than those of other treatments. SMBC and SMBN were positively correlated with organic carbon, available potassium and nitrate nitrogen, and had a significantly positive correlated with soil water content. (3) The activities of soil sucrase and catalase in 0—20 cm under W2 was the highest, following by W1 and W0, and the differences between different water treatments were significant. Under the same water management condition in wheat season, the activities of sucrase and catalase in 0—20 cm soil layer were the highest under F2, which were significantly higher than that of F1. The activities of soil sucrase, alkaline phosphatase and catalase were positively correlated with the available K and available Pin 0—20 cm soil layer, while soil sucrase, urease and catalase activities were positively correlated with soil water content in 0—40 cm soil layer. (4) The yield of wheat under F2W2 was the highest, and the differences in uptake of total N, P and K were significantly compared with other treatments. The yield and the uptake of N, P and K were significantly positively correlated with the activities of sucrase, urease and catalase, and the contents of SMBC and SMBN. Therefore, irrigation at jointing and flowering stages of wheat combined with maize fertilization with subsoiling could effectively accelerate soil nutrient activation, improve soil quality and ensure sustainable of soil production.