Gestational exposure to ambient air pollution has been associated with Congenital Heart Diseases (CHDs). However, only a few studies, with inconsistent results, have investigated the effects of PM2.5 exposure during early pregnancy. This study aims to evaluate the association between prenatal exposure to PM2.5 and CHDs occurrence. We selected 782 births reported to have CHDs between 2007 and 2014 from the Taiwanese Birth Registry and randomly selected 4692 controls without any birth defects using a population-based case-control design. Data of exposure to ambient air pollutants, mainly PM2.5, PM10, CO, SO2, NO2, and O3 during weeks 3–8 of pregnancy were retrieved from air quality monitoring stations and interpolated to every township using ordinary kriging. We applied unconditional logistic regression models adjusted for potential confounders to evaluate the associations. The results revealed a positive correlation between increased PM2.5 exposure (adjusted odds ratio aOR = 1.21, 95% confidence interval CI = 1.03–1.42, per interquartile range change = 13.4 μg/m3) during early pregnancy and overall CHDs occurrence. Furthermore, we found that atrial septal defect (aOR = 1.43, 95% CI = 1.01–2.02), endocardial cushion defect (aOR = 2.37, 95% CI = 1.01–5.58), and pulmonary artery and valve stenosis (aOR = 1.71, 95% CI = 1.06–2.78) were significantly associated with PM2.5 exposures. No similar effects were observed for the other air pollutants. This study has demonstrated some positive associations between increased PM2.5 exposure during the critical period of cardiac embryogenesis and certain CHDs occurrence. Display omitted •Prenatal exposure to air pollution increases the risk of congenital heart diseases (CHDs).•Studies on the effects of PM2.5 were limited at an exposure range higher than the WHO air quality guidelines.•PM2.5 exposure during weeks 3–8 of pregnancy increased the risks of overall and some subtypes of CHDs occurrence in Taiwan.•Results provide crucial information about the effects of PM2.5 on CHDs applicable to the majority of the global population.