Abstract: Studying the effects of straw mulching, milk vetch mulching and their synergistic mulching on wheat yield, soil nutrient and enzyme activity in the rain-fed farmland in southwest China is of great theoretical and production guiding significance for maintaining the balance of soil nutrients and optimizing the conservation tillage measures in the rain-fed farmland of southwest China. In this study, the wheat field with a "wheat/ maize/ bean" triple cropping system was taken as the research object, with 4 treatments inculding maize straw mulching (S), milk vetch mulching (A), synergistic mulching of maize straw and milk vetch (S + A), and control (CK). The results showed that compared with the CK treatment, the treatments of S and S + A significantly promoted the contents of soil total organic carbon, total nitrogen, total phosphorus, rapidly and slowly available potassium. Moreover, the A treatment obviously affected the total organic carbon, total nitrogen and alkali-hydrolyzable nitrogen in soil, while the promotion effect of it on phosphorus and potassium in soil was not significant. There was a close relationship between soil enzyme activities and soil nutrients. Meanwhile, the S + A treatment could significantly improve the activities of sucrase, protease, urease, amylase and acid phosphatase in the rhizosphere and non-rhizosphere soil, but the effects of the S and A treatments on soil enzyme activities were less than that of the S + A treatment. Compared with the CK treatment, the wheat yield increase rates of the S, A and S + A treatments were respectively 5.14%, 8.79% and 13.34%, in which the S + A treatment had the highest yield increase rate. Generally, synergistic mulching of maize straw and milk vetch could significantly increase soil nutrient content and enzyme activity, promoting the wheat yield, in the mean time of help to improve agricultural production efficiency and protecting farmland ecological environment. Consequently, synergistic mulching of straw and milk vetch could be popularized as an effective conservation tillage measure in the rain-fed farmland of southwest China.