Wheat straw is a kind of potential feedstock for the production of the green liquid biofuel candidate─methyl levulinate (ML). In this study, direct conversion of wheat straw into ML catalyzed by copper sulfate was investigated. In order to improve the ML production, the lignin in wheat straw was firstly separated as the by-product by alkali pretreatment, and the components and morphological changes of the wheat straw before and after pretreatment were compared. On the basis, the ML production from the pretreated wheat straw was optimized by response surface methodology, and a higher ML yield of 23.0 wt% can be obtained under the optimal conditions of 183 ℃, 3.3 h and 0.53 g of copper sulfate. Moreover, recycling experiments of copper sulfate were conducted, and the results showed that the ML yield decreased as the runs of recycled CuSO4 increased. However, the ML yield still reached to 18.7 wt% after five times. The results of mass balances and preliminary economic analysis indicated that the developed process is more profitable than that of the traditional ML production from wheat straw. This study can provide a reference for efficient production of ML from cellulosic biomass.