Chlorophenylacetonitriles (CPANs) are an emerging group of aromatic nitrogenous disinfection byproducts (DBPs). However, their dominant precursors and formation pathways remain unclear, which hinders the further development of effective control strategies. For the first time, CPAN precursors were screened by conducting formation potential (FP) tests on real water samples from six drinking water treatment plants (DWTPs). The average overall removal of CPAN precursors across all six DWTPs was only 10%. Moreover, ozonation increased CPAN precursors by 140% on average. Fluorescence spectroscopy showed a dramatic reduction in aromatic proteins, tyrosine-like proteins, and tryptophan-like proteins following ozonation. Low-apparent-molecular-weight (AMW) (<1 kDa) substances were correlated with the CPAN FP in these samples. We therefore hypothesized that protein fragments with low AMW, such as amino acids, are important CPAN precursors during downstream chlor(am)ination. Two aromatic free amino acids, tyrosine and tryptophan, were selected to investigate the formation of CPANs during chlor(am)ination. Both amino acids were found to act as CPAN precursors for the first time. CPAN formation pathways from these model precursors were proposed based on the frontier molecular orbital theory and intermediate products identified using high-resolution mass spectrometry. This study provides a powerful theoretical foundation for controlling CPAN formation in drinking water.