The construction of strong metal–support interactions (SMSIs) represented an attractive approach to producing supported noble metal nanocatalysts possessing enhanced stability by overlayer encapsulation. The development of facile approaches capable of achieving efficient, controllable, and extensive SMSI overlayer formation, particularly under neat and ambient conditions, is a long-standing challenge. In this work, a mechanochemistry-driven pathway was deployed for efficient and controllable SMSI construction under neat and ambient conditions to customize the capsulation degree and overlayer structures toward enhanced catalysis. The reducibility of the additives and the high interaction efficiency provided by the mechanochemical treatment could afford abundant active intermediates (e.g., Ti3+ species and oxygen defects) within a short time to induce and tune the overlayer encapsulation. This facile approach could be extensively deployed to TiO2-derived nanocatalysts with diverse phases, diverse reducible metal oxides-involved systems, and different supported noble metal nanoparticles. Enhanced hydrogenation activity was achieved by the as-afforded nanocatalysts upon SMSI construction and further tuned by the encapsulation degree.