Based on LandScan population data, land use data and highway data for the Shanghai metropolitan area from 2000 to 2015, this paper studies the impact of highways on the formation of built-up areas and subcenters to explain the emergence of the urban polycentric spatial structure. The findings are as follows. (1) The dispersion of the population strengthens the polycentric spatial structure of the Shanghai metropolitan area. From 2000 to 2015, the number of subcenters increased from 72 to 118, and their area expanded from 1347 km² to 3469 km². In addition, the main centers lost 12.7% of the population share, while the subcenters gained 12.47% of the population share. (2) Highways play a significant role in promoting urban spatial expansion and the formation of subcenters in the Shanghai metropolitan area. With every 1% decrease in distance to the nearest highway, the probability of an undeveloped area becoming a built-up area increases by 1.53–6.74%, and the probability of a built-up area becoming a subcenter increases by 11.93–20.92%. The results are robust to a series of supplementary tests, such as the replacement of explained variables or explanatory variables and the adoption of instrumental variables. (3) The Chinese government plays an important role in urban polycentric spatial development. New district and development zone policies represent two important mechanisms of highways affecting urban polycentric spatial development.