To remove higher proportions of natural organic matter (NOM) in water treatment plants, over dosing of Al-based coagulant is frequently applied. However, this leads to the risk of an excess of coagulant residue in the clean water. In this study, sequential coagulation with polyaluminum chloride (PACl) and FeCl3 was proposed to improve the removal of NOM as well as to minimize residual Al. Single dosing with either PACl or FeCl3 in particular was compared with sequential coagulation, with different dosing sequences of PACl–FeCl3 (P–F) or FeCl3–PACl (F–P). At optimum dosage, sequential coagulation P–F showed twice as much dissolved organic carbon (DOC) removal from water containing algogenic organic matter, compared to single dosing of PACl and sequential coagulation F–P. However, sequential coagulation F–P was the most effective approach for humic substance removal that improved DOC removal up to >70% compared to other dosing approaches (<60%). Practical treatment with real water also showed the advantages of sequential coagulation with P–F in improving the removal of low SUVA NOM by 18% compared to the traditional single dosing of PACl. As expected, the Al residues found in both sequential coagulation (0.07 mg/L) were significantly reduced compared to single dosing with PACl (0.15 mg/L), indicating the promising application of sequential coagulation for future safe water treatment.