Ambient air pollution is a well-known risk factor of various asthma-related outcomes, however, past research has often focused on acute exacerbations rather than asthma development. This study draws on a population-based, multigenerational panel dataset from the United States to assess the association of childhood asthma risk with census block-level, annual-average air pollution exposure measured during the prenatal and early postnatal periods, as well as effect modification by neighborhood poverty. Findings suggest that early-life exposures to nitrogen dioxide (NO₂), a marker of traffic-related pollution, and fine particulate matter (PM_2.5), a mixture of industrial and other pollutants, are positively associated with subsequent childhood asthma diagnosis (OR = 1.25, 95% CI = 1.10–1.41 and OR = 1.25, 95% CI = 1.06–1.46, respectively, per interquartile range (IQR) increase in each pollutant (NO₂ IQR = 8.51 ppb and PM_2.5 IQR = 4.43 µ/m³)). These effects are modified by early-life neighborhood poverty exposure, with no or weaker effects in moderate- and low- (versus high-) poverty areas. This work underscores the importance of a holistic, developmental approach to elucidating the interplay of social and environmental contexts that may create conditions for racial-ethnic and socioeconomic disparities in childhood asthma risk.