The removal of algal organic matter (AOM) through water treatment processes is a major approach of reducing the formation of disinfection by-products (DBP). Here, the formation of DBP from AOM in karst water under different combination of potassium permanganate (KMnO₄) and polyaluminium chloride (PACl) was investigated. The effect of divalent ions (Ca²⁺ and Mg²⁺) on DBP formation was traced by AOM chemistry variations. For DBP formation after KMnO₄ preoxidation, total carbonaceous DBPs (C-DBPs) decreased by 12.9% but nitrogen-containing DBPs (N-DBPs) increased by 18.8%. Conversely, the C-DBPs further increased by 3.3% but N-DBPs reduced by 10.7% after the addition of PACl besides KMnO₄ preoxidation. The variations of aromatic protein-like, soluble microbial products-like compounds and ultraviolet absorbance at 254 nm (UV₂₅₄) were highly correlated with the formation of DBPs, which suggest aromatic substances strongly affect DBP behaviors at different treatment conditions. In the presence of divalent ions (Ca²⁺ = 135.86 mg/L, Mg²⁺ = 18.51 mg/L), the combination of KMnO₄ and PACl was more effective in controlling DBP formation compared to the situation without Ca²⁺ and Mg²⁺. Specifically, trichloromethane formation was largely inhibited compared to the other tested DBPs, which may refer to complexation of electron-donating groups via divalent ions. While Ca²⁺ and Mg²⁺ may not affect the nature of α-carbon and amine groups, so the variation of haloacetonitriles (HANs) was not obvious. The study enhances the understanding of the DBP formation patterns, transformation of carbon and nitrogen by preoxidation-coagulation (KMnO₄-PACl) treatment in algae-laden karst water.