This study aims to synthesize nano-metakaolin (NMK) through mechanical activation and to investigate the physical, chemical and microstructural changes that occur to the initial raw material. The efficiency of the activation process is affected by various process parameters as well as the mineralogy of the original material. Two different kaolin qualities were subjected to mechanical activation through high-energy ball-milling (HEBM) under various conditions. The parameters investigated were the milling speed and time. The final properties of the NMK samples produced were examined using X-ray diffraction, Fourier-transform infrared spectroscopy, laser dynamic light scattering, thermogravimetry/differential thermal analysis, Brunauer–Emmett–Teller and scanning electron microscopy analysis. Additionally, the pozzolanic activity of the fully activated samples was evaluated using the Chapelle test. The percentage of impurities contained in the initial kaolin affected the transformation into metakaolin. The milling parameters also affected the activation, contributing mainly to the particle size of the final material. Finally, concerning the metakaolin microstructure, the material showed a tendency to form stacks and agglomerates of plates due to the development of powerful static forces.