The cement industry significantly contributes to global CO2 emissions, posing several challenges for a future low-carbon economy. In order to achieve the target established by the European Sustainable Development Goals of reaching carbon neutrality by 2050, the European Cement Association (Cembureau) has devised a comprehensive roadmap based on five key approaches, referred to as the 5C strategies. Portland clinker is one of the crucial concerns, since its production emits over 60% of the cement manufacturing emissions. Therefore, supplementary cementitious materials (SCMs) to partially replace clinker content in cement have gained significant attention in providing alternatives to traditional clinker in cement production. This paper evaluates the potential of Portuguese calcined clays (CCs) as viable substitutes for clinker to enhance sustainability in cement manufacturing. More than 50 clays were characterised through chemical and mineralogical analyses to assess their reactivity and suitability for calcination using the strength activity index (SAI), along with XRD, XRF, and TGA techniques. This study investigated the calcination conditions that provide the best clay reactivity, which were subsequently used for calcination. This investigation is part of a project to evaluate the behaviour of calcined clays through mechanical, hydration, and durability properties. The findings indicate that Portuguese calcined clays exhibit promising pozzolanic activity. Furthermore, these clays could significantly reduce CO2 emissions and raw material consumption in cement production. This research underscores the potential of local calcined clays as a sustainable clinker substitute, promoting eco-friendly practices in the construction industry.