The rapid urbanization in the Belt and Road Initiative (BRI) area has aggravated the cross-regional pollution of PM_2.5 and aroused concern about the conflicts between urban development and air quality. This study aims to examine the spatial-temporal PM_2.5 variations in the BRI region, in which area many countries are undergoing rapid urbanization and the main field of future urbanization, to delineate the driving mechanism of PM_2.5 accumulation or dissipation. Previous studies have analyzed the PM_2.5 distribution at the national level, providing limited information regarding regional heterogeneity in urbanization and PM_2.5 concentrations within each country. Additionally, the regional differences in the driving mechanisms of urbanization factors on PM_2.5 concentrations have not been thoroughly investigated within the BRI areas. In this study, remote sensing raster data was combined with geographic grid units to examine variations in urbanization and PM_2.5 within the BRI region, identifying “typical regions” where urbanization could enhance PM_2.5 accumulation. The main results are as follows: i) The spatial autocorrelation of urbanization and PM_2.5 concentrations has gradually strengthened, showing consistent high-value distributions in the North China Plain, Ganges Plain and indicating a synergistic growth among emerging developing regions such as China, India, and the Persian Gulf Coast. ii) The correlation between urbanization and PM_2.5 concentrations exhibited a distinct trend of differentiation within the BRI regions. The influence of urbanization on PM_2.5 changed from agglomeration to dispersion, forming a “typical region” category composed of ten countries, including China, India, and Morocco. iii) The three main urbanization-related factors for PM_2.5 accumulation in the “typical regions” for 2005–2016 were energy pollution emission, economic activities, and human activities. By 2023, the effects of energy pollution and economic activities are expected to converge in some “typical region” countries. Targeted urban strategies and governance actions based on the different driving-types of “typical regions” in BRI have been proposed to coordinate relationship between urban construction and atmospheric environmental protection.