The objective of this study was to evaluate the effects of the character and the removal of natural organic matter (NOM) on the formation of assimilable organic carbon (AOC) and bromate during ozone disinfection. Natural waters from two locations with different dissolved organic carbon (DOC) concentrations were tested. In addition, the DOC concentration of one of the natural waters was reduced either by ion exchange (IEX) or by granular activated carbon (GAC) filtration. The resulting four water types were tested in conventional pilot-scale ozone bubble column reactors and in a bench-scale plug flow reactor with dissolved ozone dosing. For the tested waters NOM fractions were determined with size exclusion chromatography using DOC and UVA254 detection. As expected, it was observed that for the same ozone dosages the CT is higher when NOM is removed by IEX or GAC compared to the situation without NOM removal. It is concluded that, for the waters tested, removal of the humic compounds with a molecular weight of approximately 1,000 g/mol by using IEX led to less AOC formation and less bromate formation as compared to the removal of humic compounds with a molecular weight of 300–500 g/mol by using GAC.