Improving the sense of well-being of rural residents is an important goal to accelerate the modernization of agriculture and rural areas and promote the strategy of rural revitalization. The role of E-commerce and other new information technology in improving the happiness of rural residents has been widely discussed in the academic field. Based on the micro data of China General Social Survey (CGSS) and the theory of happiness economics, this paper analyzed the relationship between E-commerce and rural residents’ happiness and further discussed the mechanism by the Ordered Probit model and the intermediary benefit model. Results show that the average subjective well-being of rural residents is 3.870, which still has some room for improvement, and the happy rural residents who participate in E-commerce are 5.54% higher than those who do not. Rural residents’ participation in E-commerce activities can significantly improve their subjective well-being. E-commerce participation will bring significant welfare effects to youth and rural residents in the central and western China. Mechanism analysis shows that E-commerce participation can improve rural residents’ happiness by improving social trust and income. Therefore, this paper suggests continuing to strengthen policy support, encouraging E-commerce participation in service innovation, increasing farmers’ E-commerce skill training, and promoting the continuous improvement of rural residents’ sense of well-being.