The study examines the influence of the urban spatial structure on smog pollution and its mechanism of action using the panel data of Chinese cities from 2012 to 2017. Research suggests that the multi-center development of Chinese cities has aggravated regional smog pollution. Robustness test results support this finding. Results of the interaction term shed light on the fact that multi-center spatial development in backward regions can exert a greater influence on smog pollution. Meanwhile, suppose the research samples are divided by different zones. In that case, it can be observed that an inverted-U shape characterizes the multi-center development of regions of East China and smog pollution. This indicates that worsening smog pollution appears only as a periodical phenomenon of the pre-stage multi-center development of Chinese cities, which can be ushered into a turning point through certain paths. Analysis of the influence mechanism shows that the transport mode and the energy consumption intensity constitute two major channels for multi-center development of Chinese cities to affect regional smog pollution.