Due to greenhouse gas emissions, the production of cement clinker is considered unsustainable and many attempts are being made to replace cement with alternative materials sourced from agriculture, industry and other urban practices, such as construction and demolition works. The aim of this paper is to analyze the effects of cement substitution by locally available waste materials in Serbia, such as fly ash (FA), blast furnace granulated slag (BFGS) and wheat straw ash (WSA), up to the 50% replacement volume rate in cement–lime mortars. As the effective application of supplementary cementitious materials (SCMs) in cement-based materials requires a comprehensive insight into their properties, a characterization of materials involving all relevant physical, chemical and mechanical tests is conducted. Ten different mortar mixed with ingredients of a volume ratio 1:2:4 (cementitious powder/lime/sand) were designed and their consistency, bulk density, capillary water absorption, flexural strength, compressive strength and thermal analysis (TGA/DTA) results were examined to determine the influence of the abovementioned SCMs on mortar properties. Research findings highlight the possibility of replacing cement with slag (50%), fly ash (30%) or wheat straw ash (30%) while maintaining its performance and improving the economic and environmental impacts of masonry mortar production.