Malawi is one of the least-developed countries in Sub-Saharan Africa with disaster-prone housing infrastructure characterized by poor construction materials. Therefore, there is a need to provide resilient and cost-effective materials, such as limestone calcined clay cement (LC3). However, the exploitation of LC3 in Malawi is limited due to a lack of mineralogical information about the clays and limestone and related strength and durability when used as a cementitious material. In this study, the strength and physico-chemical properties of LC3 systems with 50% and 40% clinker contents (LC3-50 and LC3-40) were investigated. Cement mortar specimens were prepared at water to cement (w/c) ratios of 0.45, 0.5, and 0.6 with varying calcined clay (CC) to limestone (CC/LS) ratios (1:1, 2:1, and 3:1). The effects of CC/LS ratio on the fresh properties, strength, and durability were investigated. The results showed that specimens with 40% Portland cement replacement levels (LC3-40) exhibited higher standard consistency (up to 45%) than LC3-50, porosity in the range of 8.3–13.3%, and maximum water uptake in the range of 3.8–10.9%. On the other hand, LC3-50 samples offered the highest strength of approximately 40 MPa, complying with requirements for pozzolanic cementitious materials, whereas LC3-40 conforms to the strength requirements for masonry cements. This work shows that LC3 systems can be manufactured with local clays and limestone available in Malawi, and used as a sustainable construction material to mitigate carbon emissions as well as boost the local economy.