The thermally activated clay minerals are well-known as perspective supplementary cementing materials (SCMs) able to reduce the Portland clinker consumption and thus also the related CO2 emissions. The best SCM performance among clay minerals is provided by thermally activated kaolin (metakaolin). Nevertheless, kaolinitic clays are not available everywhere, while varying mixed clays can be considered as globally affordable raw materials. The present work deals with the thermal activation of four illitic-kaolinitic clays with varied content of clay minerals, quartz and calcite, available locally in the Czech Republic. The attainment of activation was evaluated with the help of mechanical strength and the saturated lime test. There is no doubt that kaolin is the best clay for SCM production. However, the activation of mixed illitic-kaolinitic clays at 600 °C provided comparable and sufficient performance, despite that the crystal structure of illite was not completely decomposed. The non-clay minerals presence did not reduce the activity either; even the clay containing just about 50% of clay minerals (mostly illite) treated at 650 °C provided sufficient mechanical performance. As the drawback of activated illitic clays must be considered their higher sensitivity to the proper calcination temperature compared to metakaolin since illite (and other 2:1 clay minerals) does not form any metastable dehydroxylated phase.