In the arid region of Northwestern China, development of oasis agriculture is directly influenced by the climate change impacting on area temperature, precipitation, water supplies and so on. The present research focuses on how to maximize the efficiency of economic-society-ecology through adjusting the crops in the middle-reaches of the Heihe river basin for the development of the regional sustainable agriculture. With the boundary condition of land resources, crop planting area, food security, farmer-income protection, and ecological pressure, the study developed a linear programing model based on the purpose of profit-maximization. The result indicated that the net value of agricultural output may increase 1 152 million Yuan as well as agricultural water-saving of 27.9%, if the plantations of main food and economical crops and other crops are adjusted from 39.96%, 37.71%, and 22.33% to 40.13%, 39.96%, and 19.91%, respectively under the situation of 0.41% reduction in crop planting area.