Current studies on air pollutant exposure during pregnancy and orofacial clefts (OFCs) have inconsistent results, and few studies have investigated refined susceptible windows for OFCs. We aim to estimate association between air pollution and OFCs during the first trimester of pregnancy and identify specific susceptible windows. Birth data was obtained from Birth Defects Surveillance Network in Lanzhou from 2014 to 2019. Air pollution data and temperature data were obtained from ambient air monitoring stations and China Meteorological Data Network, respectively. A distribution lag nonlinear model (DLNM) was applied to estimate weekly-exposure-lag-response association between air pollutant levels and OFCs. The study included 320,787 perinatal infants from 2014 to 2019, of which 685 (2.14‰) were OFCs. The results demonstrated that exposure of pregnant women to aerodynamic diameter ≤ 10 μm (PM(10)) at lag 4-5 weeks was significantly associated with the risk of OFCs, with the greatest impact at the lag 4 week (RR = 1.029, 95% CI = 1.001-1.057). Exposure to sulfur dioxide (SO(2)) at lag 2-4 weeks was significantly associated with the risk of OFCs, with the greatest impact at the lag 3 week (RR = 1.096, 95% CI = 1.041-1.177). This study provides further evidence that exposure to air pollution increases the risk of OFCs in the first trimester of pregnancy.