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Due to developmental toxicity, prenatal exposure to per- and polyfluoroalkyl substances (PFASs) in animals may result in adverse effects on the fetus. However, little information is available on PFASs presence in the human cord plasma. Here, we measured the levels of 37 emerging and legacy PFASs in 650 cord plasma samples collected every 5 years spanning 1998 to 2018 by the Beijing Cord Blood Bank and evaluated changes in PFASs concentrations using generalized additive models. We observed an increase in the concentrations of 24 PFASs (Σ 24 PFASs) from 1998 to 2003 followed by a decrease every 5 years from 2003 to 2018. For legacy PFASs, similar trends were observed for PFOS, whereas PFOA levels did not decline until 2013. For emerging chemicals, 6:2 Cl-PFESA showed a similar trend as PFOS, and prenatal exposure to 6:2 Cl-PFESA could be traced back to 1998, with a median concentration of 0.411 ng/mL in plasma. Our data showed that prenatal exposure to legacy PFASs has gradually decreased in cord plasma from the Beijing Cord Blood Bank in recent years, and the discovery of the presence of emerging chemicals in 1998 suggested that further evaluation is needed to assess possible health risks to pregnant women and fetuses.