The aim of this study was to investigate the fate of natural organic matter (NOM) and subsequent changes during the various treatment processes at a full-scale Drinking Water Treatment Plant (DWTP). Monthly sampling campaigns were conducted for 1 year at six sites along DWTP of Thessaloniki, Northern Greece including raw water from the Aliakmonas River that supplies DWTP and samples from various treatment processes (pre-ozonation, coagulation, sand filtration, ozonation, and granular activated carbon (GAC) filtration). The concentration of NOM and its characteristics as well as the removal efficiency of various treatment processes on the basis of dissolved organic carbon, UV absorbance, specific ultra-violet absorbance, fluorescence intensity, hydrophobicity, biodegradable dissolved organic carbon, and formation potential of chlorination by-products trihalomethanes (THMs) and haloacetic acids (HAAs) were studied. The concentration of dissolved organic carbon (DOC) in reservoir of the Aliakmonas River ranged from 1.46 to 1.84 mg/L, exhibiting variations regarding UV, fluorescence, and hydrophobic character through the year. Along DWTP, a significant reduction of aromatic, fluorophoric, and hydrophobic character of NOM was observed resulting in significant elimination of THM (63 %) and HAAs (75 %) precursors.