Setting up React for ES6 with Webpack and Babel allows developers to build reusable UI components and maintain state changes in a Single Page Application. Facebook's efforts to keep React up-to-date have made it compatible with new features from ECMAScript 6 (ES6), but browser support for ES6 is not widespread, making tools like Babel necessary. By installing NodeJS, npm, React, Webpack, and Babel, developers can create components using ES6 syntax and JSX, which is then transpiled to ES5 code for browser compatibility. With the help of Webpack's loader pipeline, developers can bundle their code into a single file, making it easier to serve their application. By following these steps, developers can build complex Single Page Applications with React, overcoming the hurdle of integrating new technologies and creating awesome applications.