Experiments and field observations have shown that supplementary cementitious materials (SCMs) mitigate the risk of alkali-silica reaction (ASR) in Portland cement blends, but this is difficult to describe thermodynamically due to the lack of appropriate thermodynamic database information, and challenges in defining the kinetic factors. This paper examines how four well-known SCMs (namely ground granulated blast furnace slag, silica fume, metakaolin, and fly ash) mitigate ASR, by using a multi-stage simulation and a newly extended thermodynamic database. Calcium hydroxide consumption by SCM hydration, dilution of available alkalis, and alkali binding in calcium-alkali-aluminosilicate hydrate solid solutions, play pivotal roles in understanding the influence of SCMs in ASRs. Blending aluminium-rich SCMs in ASR-prone systems appears to act by preventing the dissolution of reactive silica in aggregates rather than by suppressing the formation of ASR products. This paper provides new thermodynamic insights into the mechanisms by which SCMs enhance concrete durability against ASR.