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Ambient pollutants are associated with clinical and sub-clinical indicators of infertility, such as poor sperm quality. However, the link between the ambient fine particle (PM2.5) concentration and the fertility rate (FR) is unclear. In this epidemiological study, we examined the association between PM2.5 concentration and childlessness in the United States (US). We conducted a nationwide spatiotemporal study of ~29 million births in 520 US counties from 2003 to 2011. We obtained monthly numbers and demographic data of newborns from the Centers for Disease Control and Prevention, and PM2.5 estimates from a downscaling model of in situ observations and outputs from the Community Multiscale Air Quality Model. We evaluated the association between the mean PM2.5 concentration and the FR during the gestational (0–8 months before birth) and pre-gestational (9–11 months before birth) periods using a Poisson model with demographic and socioeconomic covariates. We found a significant association between the FR and PM2.5 exposure during pre-gestation but not gestation. Each 5 μg/m3 increase in pre-gestational PM2.5 exposure was associated with a 0.7% (0.0%, 1.4%) reduction in the FR. Nonlinear analysis suggested a sublinear association between the reduction in the FR and PM2.5 concentration without a safety threshold. Additionally, an annual mean reduction of 1.16 (1.15, 1.17) births per 1000 females aged 15–44 years was attributable to PM2.5. This study established, for the first time, an association in the US between the FR and PM2.5 concentration, a finding that adds to the extant epidemiological evidence of the effects of ambient pollutants on fertility, and extends the scope of the impact of low air quality on health. Keywords: Fine particulate matter, PM2.5, Fertility rate, Spatiotemporal epidemiology, Childlessness