The mechanisms of rhodium‐catalyzed coupling reaction of ketoxime and 1,3‐enynes were investigated by using density functional theory calculations. Different 1,3‐enynes would lead to different annulation products. Reaction A undergoes five sequential steps (CH activation, 1,3‐enyne migratory insertion, 1,4‐Rh migration, cyclization, and deprotonation) to lead to the [4 + 1] annulation product, whereas due to the electronic effect, the process generating the [4 + 2] product in reaction A is restricted. In contrast, the electron‐withdrawing group of the N(Me)2 group in 1,3‐enyne would bring about the [4 + 2] annulation product in reaction B. Our calculated results indicate that no [4 + 1] annulation product could be obtained in reaction C, in agreement with the experimental observation that the cis‐allyl hydrogen in 1,3‐enyne is crucial for the [4 + 1] annulation reaction.