The water-economy-innovation nexus is an integrated system that plays an important driving role in urban and regional sustainable development. To identify, evaluate, and measure the coupling-coordinated development of the regional water-economy-innovation nexus, this study selects China’s Grand Canal area as a typical case and constructs an integrated evaluation system of the water-economy-innovation nexus. Then, the coupling coordination model is used to evaluate the regional water-economy-innovation nexus’ development. Finally, grey correlation analysis is used to evaluate the influencing factors. The results find that the water-economy-innovation nexus’ overall development level is not high and that there are significant spatial differences. The coupling coordination level keeps rising, and the coupling coordination level of the central city is obviously better than other cities. Water accounts for the largest contribution to the coupling coordination of the water-economy-innovation nexus, followed by economy and innovation. This study contributes to the knowledge body of sustainable development and provides a scientific basis for the decision of coupling the development of the water-economy-innovation nexus in China’s Grand Canal area and other regions.