This study was to investigate the association between trimester-specific exposure to air pollutants and the risk of Birth defects (BDs) among Chinese births. A time-dependent Cox proportional hazards model was used to explore the associations between trimester-specific and entire pregnancy concentrations of the pollutants and BDs at Changsha, China from 2014 to 2018. Each increment in ambient particles with diameters of 2.5 μm or less (PM_2.5) concentrations was associated with a higher risk of BDs with an hazards ratios (HR) [95% confidence intervals (CI)] between 1.06 (1.03–1.09) and 1.39 (1.27–1.53) during the entire pregnancy period. This association was also pronounced for ozone (O₃) with an HR (95% CI) between 1.03 (1.00–1.06) and 1.23 (1.15–1.31) over the entire pregnancy. Elevated risks of BDs were found to be linked to sulfur dioxide/nitrogen dioxide (SO₂/NO₂) exposure during the first trimester, carbon monoxide (CO) exposure during the second trimester, and particulate with diameters of 10 μm or less (PM₁₀) during the third trimester of pregnancy. For subtype analyses, PM_2.5 exposure exhibited a significant association with a variety of BD types, especially nervous system defects with an HR (95% CI) between 1.13 (1.03–1.24) and 1.19 (1.09–1.31), PM₁₀ was associated with complex defects and nervous system defects, O₃/SO₂ was associated with all types of BDs except cardiac defects, NO₂ was associated with nervous system defects, and CO was associated with unclassifiable defects. The study adds to evidence on the association between maternal exposure to air pollutants and BDs and has implications for public health policy.