The occurrence of smectite-illite and smectite-chlorite minerals series was studied along a thick clay cap (~300 m) drilled in the Cerro Pabellón geothermal field (northern Andes, Chile). X-ray diffraction (XRD) and scanning electronic microscopy (SEM) were used to characterize the alteration mineralogy and clay mineral assemblages and their changes with depth. Cerro Pabellón is a high-enthalpy blind geothermal system, with a reservoir zone from ~500 m to 2000 m depth, with temperatures of 200–250°C. Three main hydrothermal alteration zones were identified: (1) argillic; (2) sub-propylitic, and (3) propylitic, with variable amounts of smectite, illite-smectite, chlorite-smectite, mixed-layer chlorite-corrensite, illite and chlorite appearing in the groundmass and filling amygdales and veinlets. Chemical and XRD data of smectites, I-S and illites show, with some exceptions, a progressive illitization with depth. The evolution of I-S with depth, shows a sigmoidal variation in the percentage of illite layers, with the conversion of smectite to R1 I-S at ~180–185°C. These temperatures are greater than those reported for other similar geothermal fields and might indicate, at least in part, the efficiency of the clay cap in terms of restricting the circulation of hydrothermal fluids in low-permeability rocks. Our results highlight the importance of a better understanding of clay-mineral evolution in active geothermal systems, not only as a direct (or indirect) way to control temperature evolution, but also as a control on permeability/porosity efficiency of the clay cap.