Density functional theory (DFT) calculations were employed to elucidate the mechanism and selectivity of nickel-catalyzed defluorinative asymmetric cyclization reactions of trifluoromethyl-substituted 1,6-enynes. The results indicate that the product is formed via a stepwise addition cyclization mechanism, including sequential steps of ligand coordination, transmetalation, ligand exchange, alkyne insertion, olefin insertion, β-F elimination, another transmetalation, and a final ligand exchange. The regioselectivity is primarily governed by the alkyne insertion step, where electrostatic interactions strongly favor 1,2-insertion of the carbon-carbon triple bond over 2,1-insertion. The enantioselectivity is largely determined during the insertion step of the olefin insertion step, with the (S)-product forming preferentially over the (R)-product due to stronger non-covalent interactions between the ligand and the substrate, minimal catalyst conformational distortion, and enhanced electronic interactions between the catalyst and the substrate.