Accumulating studies have been focused on the independent effects of air pollutants and ambient heat exposure on congenital heart defects (CHDs) but with inconsistent results, and their interactive effect remains unclear. A case-control study including 921 cases and 9210 controls was conducted in Changsha, China in warm season in 2015-2018. The gravidas were assigned monthly averages of daily air pollutants and daily maximum temperature using the nearest monitoring station method and city-wide average method, respectively, during the first trimester of pregnancy. Multivariate logistic regression models were used to estimate the independent effects of each air pollutant and different ambient heat exposure indicators. Their additive joint effects were quantified using attribute proportions of interaction (API). Increasing SO(2) consistently increased the risk of CHDs in the first trimester of pregnancy, with aORs ranging from 1.78 to 2.04. CO, NO(2) and PM(2.5) exposure in the first month of pregnancy, and O(3) exposure in the second and third month of pregnancy were also associated with elevated risks of CHDs, with aORs ranging from 1.04 to 1.15. Depending on the ambient heat exposure indicator used, air pollutants showed more apparent synergistic effects (API > 0) with less and moderately intense heat exposure. Maternal exposure to CO, NO(2), SO(2), PM(2.5) and O(3) during early pregnancy increased risk of CHDs, and ambient heat exposure may enhance these effects. Our findings help to understand the interactive effect of air pollution with ambient heat exposure on CHDs, which is of vital public health significance.