Ni(COD)2-catalyzed cycloaddition reactions to access pyridines have been extensively studied. However, this catalyst typically requires drying procedures and inert-atmosphere techniques for the reactions. Herein, we report operationally simple nickel(0) catalysis to access substituted pyridines from various nitriles and 1,6-diynes without the aid of air-free techniques. The Ni-Xantphos-based catalytic manifold is tolerant to air, moisture, and heat while promoting the [2 + 2 + 2] cycloaddition reactions with high reaction yields and broad substrate scope. In addition, we disclose that not only the steric effect but also the frontier molecular orbital interactions can play a critical role in determining the regiochemical outcome of nickel-catalyzed [2 + 2 + 2] cycloaddition for the synthesis of substituted pyridines.