The fresh behavior of Ordinary Portland cement (OPC)-Metakaolin (MK) cementitious material system is relatively undesirable and needs to be used in conjunction with other materials and comprehends interaction mechanism to meet practical application specifications. The present work investigated the feasibility of using fly ash (FA) to modify the properties of MK cement and reported the effects of the interaction between MK and FA on the microstructure and hydration products. The results showed that the fluidity loss behavior and premature setting time for the cement-MK system was improved by adding the appropriate amount of FA. Synergistic stacking and hydration effect of FA and MK in the ternary blend significantly yielded a more uniform mix, resulting in a matrix with a higher compressive strength and more compact structure. Besides, the addition of FA contributed to reduce the typical hydration product Ca/Si ratio and promoted the ability of gel products to absorb Al3+, which was beneficial to the Al-rich system such as OPC-MK system. This research provides the foundation for the long-term development of multi-based supplementary cementitious materials (SCMs).