The combined use of calcined clay and limestone (LC2) with slag cement can ease the promotion of a clay-type binder and elongate the use of traditionally used slag. Results showed that addition of 22–39% LC2 can enhance the compressive strength of slag cement concrete by 26, 86, 39 and 24% at 3, 7, 28 and 90 days, respectively. Quantitative X-ray radiation diffractometry (QXRD), thermogravimetry analysis (TGA), calorimetry and thermodynamic modelling have been used to reveal the individual role of each constituent in the quaternary blend. Results showed that the degree of hydration of slag cement can be increased by LC2, and calcined clay was understood to be the main contributing factor owing to the pozzolanic reactivity and filler effect. Limestone can increase the reaction degree of slag owing to the generation of hydrated mono-/hemi-carboaluminate (Mc/Hc). A synergistic effect of slag and limestone can contribute to the later performance in quaternary LC2–slag cement.