Metal nanoclusters are becoming exciting candidates as highly efficient catalysts for heterogeneous processes in view of their extraordinary surface to volume ratio and the high concentration of uncoordinated atoms that contribute to enhanced catalytic activity. For this reason, the development of accurate and reliable procedures for the synthesis of stable and supported metal nanoclusters is highly desirable. Although Ag nanoclusters (Ag NCs) stabilized by anion templates with a structure like Ag-m+n(m+) and a long lifetime have been widely investigated, supported clusters present significant advantages regarding their recovery and recyclability. In spite of their potential, the stabilization of clusters of precious metals on porous substrates is scarcely investigated. Herein, we present an innovative approach for the synthesis of stable Ag nanoclusters designed with the aim of achieving a strict control of key phases such as mixing, microwave heating, and quenching. The catalyst was used for the activation of alkynes showing excellent activity for the formation of C-O, C-N, and C-C bonds. When compared with commonly used homogeneous Ag salts, Ag NCs enhanced the catalytic activity toward the cyclization of a wide range of substrates, thereby minimizing the metal loading and allowing the separation as well as the reuse of the catalyst for multiple cycles.