Dissolved organic matter (DOM) causes organic pollution in lakes, resulting in the occurrence of off-flavour etc. when lake water is used as a drinking water source. In this study, DOM in 11 major lakes in Japan was characterised by high-resolution Orbitrap mass spectrometry. Molecular formulas were assigned to 845–1,451 components per sample. Among them, 555 components were commonly found in all lakes. The DOM compositions of the 11 lakes were clustered into four groups. Correlation analysis could extract specific components whose relative intensities were associated with water quality indices such as specific ultraviolet absorbance, specific dissolved chemical oxygen demand (DCODMn), and specific trihalomethane formation potential (R = 0.80–0.93, p < 0.05). Although further molecular structural analyses of DOM components are necessary, these results could be informative for exploring key candidates related to specific water quality issues. Pre-treatment of samples with permanganate oxidation was applied to screen components which could contribute to DCODMn. DCODMn components accounted for only 7–30% of total peak intensities, indicating the limited performance of permanganate oxidation. Pre-treatment by permanganate coupled with Orbitrap MS revealed that components with higher molecular weight, higher oxygen-to-carbon ratios (O/C), and lower hydrogen-to-carbon ratios (H/C) could be responsible for DCODMn.