Although thermal and mechanochemical activations of natural clays are well-documented, there exists a dual research gap. Firstly, a thorough investigation into the interrelationship between these activation methods and the governing parameters of reactivity for various clays has been notably lacking. Secondly, there is a distinct scarcity of studies specifically focusing on heterogeneous clays compared to the extensive research dedicated to single-layer clays specially kaolinitic clays. This study investigates the correlation of activation methods, and changes in the clay mineralogy, particle size distributions, morphology, specific surface area, and the reactivity of heterogeneous clays. Traditional thermal and mechanochemical activation methods often fall short in achieving complete dehydroxylation of heterogeneous clay minerals and improving their reactivity beyond predefined low thresholds. The results in this paper emphasize that, despite these limitations, combining these activation methods brings about significant modifications in crucial parameters. Notably, integrating 20 minutes of mechanochemical activation at 500 rpm with prior thermal treatment leads to 158% increase in specific surface area compared to mechanochemical activation conducted on un-calcined clays. Simultaneously, these combined activations result in up to 127% improvement in reactivity levels of heterogenous clays compared to standalone mechanochemical activation. The results underscore that, even with the advancements brought about by combined activations, the presence of impurities like iron oxides and calcite remains a noteworthy factor influencing the reactivity of kaolinitic natural clays. The study concludes by highlighting the potential of combined treatments to enhance the pozzolanicity of low-reactive heterogeneous clays, unlocking avenues for future clinker supplementation with this abundant resource.