Seawater-mixed concrete (SWC) is a proposed solution for catering to the needs of developing nations facing extremely severe water stress. Recent research works advocate the feasibility of producing SWC by adding supplementary cementitious materials (SCMs) and alternative reinforcements without reducing the engineering properties of the same. However, limited information is available for optimising the type and amount of SCMs in binary and ternary blended SW-mixed cementitious systems for achieving desirable strength development and early-age hydration. A comprehensive study to understand the evolution of heat of hydration and strength up to 28 days was conducted on 31 binder compositions mixed with both fresh water (FW) and seawater (SW). Fly ash, slag, metakaolin, and limestone are the supplementary cementitious materials used with CEM I as a primary binder at a replacement level between 10 and 70%. Isothermal calorimetry results revealed an increase in total heat of hydration and a reduction in setting time with SW-mixed cement pastes compared to their FW-mixed counterparts. Similarly, a significant increase in strength between 0 and 50% was observed in SW-mixed cement pastes. Suitable binder combinations showing an increase in compressive strength and not a significant reduction in strength compared to the CEM I reference mix were identified using the strength improvement factor approach. Binary and ternary blended cementitious, consisting of fly ash, slag, and metakaolin at different replacement levels, are amongst the chosen binder combinations.