Water scarcity is one of the greatest challenges to the coordinated development of the Beijing-Tianjin-Hebei (BTH) city region. This study thus investigates the optimized industrial structure and potential benefits of the BTH city region under the water resource constraint by developing a multi-city and multi-objective optimization model. The results verify that benefits in terms of economic growth and water savings are simultaneously achievable through the industrial restructuring, with an economic growth potential of Chinese Yuan (CNY) 302 billion and potential water savings of 8760 million m3. To achieve this “optimized” status, the output scale of the BTH city region should increase by CNY 1246 billion and the regional industrial structure be optimized by restricting the scale of water-intensive sectors and supporting technology-intensive industries. This study also emphasizes the significance of agricultural water use control in Hebei for water saving and suggests reconsidering the traditional positioning of Hebei as a national grain production base. The results provide useful information for the adjustment of the industrial structure of the BTH city region and are thus conducive for relevant policy formulation.