The sustainable economic development of the Yangtze River Economic Belt is a significant part of China’s regional development strategy. The article selects panel data from 11 provinces of the region from 2004 to 2020 and constructs a spatial economic model and a threshold effect model to investigate the impact of energy development and technological innovation on the real economy of this region. The result indicates that technological innovation plays a significantly beneficial role in supporting the development of the local real economy, while its spatial spillover effect to neighboring provinces is not significant. Energy development has a significant negative impact on both the local real economy and that of the neighboring provinces. Such impact is shaped by the threshold effect of the level of technological innovation.