The Yangtze River is significantly impacted by industrial activities related to per- and polyfluoroalkyl substances (PFAS) in China, posing potential threats to drinking water safety. So far, our knowledge of PFAS occurrence in the river and their fate in the whole drinking water supply systems remains limited. We conducted a comprehensive investigation of PFAS in Jiangsu's drinking water systems, using the target screening method. 12 perfluoroalkyl acids (PFAAs) and 7 emerging PFAS were detected and precisely quantified in the whole treatment process water flows, as well as source water and household tap water with concentrations of 61.34–90.40 ng/L. PFAAs [PFOA (30.26 ng/L), PFBS (23.25 ng/L), PFBA (18.82 ng/L) and PFHxA (16.89 ng/L)] and 8:8 PFPiA (13.63 ng/L) were the dominant pollutants in the low Yangtze River. PFBA (19.92 ng/L), PFBS (15.02 ng/L) and PFOA (11.94 ng/L) were major contaminants in tap water. The powder activated carbon pre-treatment in DWTP-B could remove 21.36–65.84% of long-chain PFAS, especially PFOA. Ozonation achieved slight emerging PFAS removal (3.22–11.06%), while PFAAs concentrations exhibited an increase. Granular active carbon filtration was effective in removing long-chain PFAS, with DWTP-B outperforming DWTP-A. PFSAs (3.12–22.09%) had a better removal than PFCAs (− 0.62 to 19.54%). Infants and children face a moderate health risk of PFAS intake through drinking water, peaking at the age group of 9 months to 1 year (HQ = 2.45). These findings underscore the necessity for improved PFAS removal technologies and stricter regulation of PFAS contamination in the Yangtze River to reduce exposure.