Calcined clays are used as a supplementary cementitious material (SCM) because, as hydrated aluminosilicates of the phyllosilicate group, they can be activated thermally, promoting dehydroxylation and structural disorder, i.e. making them reactive. The main effect of using calcined clay as an SCM is that CO2 emissions into the atmosphere are reduced by the reduction in the clinker/cement factor due to substitution of a proportion of clinker by calcined clay. Clays rich in kaolinite (1:1) group minerals offer most promise in terms of thermal activation. However, increased costs caused by demand for kaolinite from other industries means that type 2:1 calcined clays and mixtures of them have begun to be investigated as possible pozzolanic materials. The physical, chemical, and mineralogical characteristics that control the performance of these calcined clays as SCMs are still under discussion. Few in-depth studies of the behavior of these characteristics have been reported. The origin and geological history of raw materials, as well as their impact on the thermal activation and performance as SCM, are not well understood or, in some cases, have not been considered. The objective of the current work, therefore, was to study multicomponent clays from metamorphic rocks with low-grade kaolinite (<50%) from a tropical region of Colombia for possible use as SCMs. The clay deposit was identified by geological exploration techniques and classified in depth according to horizons of the weathering profile. The samples were extracted from the first 50 m of the deposit and characterized physically, chemically, and mineralogically; they were calcined at 650, 750, and 850°C; their degree of alteration was estimated by the Chemical Index of Alteration (CIA); and their performance as an SCM was evaluated by the Strength Activity Index (SAI) and Frattini test. As a main result, a relationship was found between the weathering profile of the deposit and the CIA of raw clays, which confirmed the high weathering and degree of alteration of the parent rock in the deposit (weathered rock and residual soil with a CIA > 80%). Furthermore, pozzolanic (physical and chemical) tests demonstrated the potential use of calcined clays from this deposit as SCMs, as well as their thermal activation at low temperature (≤750°C). In addition, the pozzolanic activity increased with the kaolinite/(muscovite+illite+vermiculite) ratio mainly, and, in turn, the thermal activation temperature increased with the mica and type 2:1 clay content.