Mechanism driven catalyst design with atomically uniform ensemble sites is an important yet challenging issue in heterogeneous catalysis associated with breaking the activity-selectivity trade-off. Herein, a trimer Ni1Sb2 site in NiSb intermetallic featuring superior selectivity is elaborated for acetylene semi-hydrogenation via a theoretical guidance with a precise synthesis strategy. The trimer Ni1Sb2 site in NiSb intermetallic is predicted to endow acetylene reactant with an adequately but not excessively strong σ-adsorption mode while ethylene product with a weak π-adsorption one, where such compromise delivers higher ethylene formation rate. An in-situ trapping of molten Sb by Ni strategy is developed to realize the construction of Ni1Sb2 site in the intermetallic P63/mmc NiSb catalysts. Such catalyst exhibits ethylene selectivity up to 93.2% at 100% of acetylene conversion, significantly prevailing over the referred Ni catalyst. These insights shed new lights on rational catalyst design by taming active sites to energetically match targeted reaction pathway.