Abstract: As the key factors to promote the high-quality development of the Yangtze River Economic Belt (YREB), scientific and technological innovation and population agglomeration have an important impact on the Chinese-style modernization. Therefore, using the panel data of 110 cities at or above the prefecture level in the YREB from 2010 to 2021, this paper empirically analyzed the spatial correlation network between scientific and technological innovation and population agglomeration and the mechanism of population agglomeration on scientific and technological innovation. The results showed that: (1) Most cities in the YREB were in the central position, but their rankings in the two correlation networks were quite different; The spillover effect of provincial capital city in the spatial correlation network of science and technology innovation was significant. (2) Population agglomeration in the YREB was not conducive to improving the level of scientific and technological innovation. The development of R&D personnel and service industry was conducive to improving the level of scientific and technological innovation, while economic development also inhibited scientific and technological innovation. (3) From the perspective of the diverging segment, the upstream population agglomeration significantly promoted the scientific and technological innovation, but inhibited the scientific and technological innovation in the surrounding cities; The population agglomeration in the middle reaches was not conducive to scientific and technological innovationand the surrounding cities. The downstream population agglomeration had a potential supporting effect on the regional science and technology innovation, and the positive spillover effect on the surrounding cities was significant. The development of R&D personnel and service industries in the upper, middle and lower reaches was conducive to scientific and technological innovation. To this end, all localities should implement local policies, optimize the talent incentive mechanism, and guide the population to gather rationally in order to achieve high-quality coordinated and balanced development of scientific and technological innovation in the YREB.