During rapid urbanization, microclimate environment deterioration through events such as haze pollution and heat waves has continuously occurred in cities, which greatly affects the living environment, production activities, and health of urban residents. Therefore, it is particularly necessary to explore methods for controlling and optimizing the urban microclimate environment. In this paper, based on the mechanism of the effect of urban spatial structure at street-level on the distribution of atmospheric particulate matter, an indicator system that can be employed to comprehensively describe and quantify urban morphological structure at street-level was constructed from eight aspects: the spatial morphology of street-valleys, intensity of land use and development, geometric structure of buildings, inhomogeneity of buildings, roughness of the underlying surface, distribution of ecological landscapes, 3D architectural landscape morphology, and ventilation potential. Furthermore, using satellite remote sensing images and vector thematic maps of Shanghai, indicator factors were quantified by applying GIS technique. The intrinsic mechanism of the influence of the urban morphology on the diffusion and transport of atmospheric particulate matter was comprehensively analyzed by combining statistical methods and data mining algorithm, and eight key dominant factors were identified that can be considered to improve the urban ventilation conditions and help control urban air pollution, namely, the land use intensity, urban canopy resistance, vegetation cover, spatial congestion rate, comprehensive porosity, height-to-gross floor area ratio, building density, and average building volume ratio. As such, according to the quantitative analysis results for various combinations of the dominant factors, a spatial optimization strategy at street-level that can help improve the urban air quality was proposed in terms of identifying the pathways through which urban spatial elements affect the distribution of particulate matter, i.e., controlling the source–flow diversion–flow convergence process.