The density functional theory method augmented with the CPCM solvation model was used to study the mechanism of Cu(I)-catalyzed aryl amidation. On the basis of the comparison of multiple reaction pathways, it was determined that diamine-ligated copper(I) amidate was the most reactive intermediate in the reaction mixture for the oxidative addition to aryl halide. Cationic diamine-ligated Cu(I) was calculated to have a lower free energy barrier for oxidative addition, but its concentration in the reaction mixture was too low to represent a useful catalyst. On the other hand, multiple ligation of the amide to Cu(I) at low diamine concentration led to the least reactive intermediate and, thereby, retarded the oxidative addition. Further calculations showed that oxidative addition was the rate-limiting step in Cu-catalyzed aryl amidation. Unlike the transformation from Pd(0) to Pd(II), the Cu(I) → Cu(III) oxidative addition product was pentacoordinated and, thereby, more sensitive to the steric hindrance. A major portion of the overall energy barrier in the oxidative addition to Cu(I) was contributed by the highly unfavorable formation of a 2η complex between copper(I) amidate and aryl halide. Reductive elimination occurred through a square pyramidal structure from the pentacoordinated Cu(III) intermediate. Reductive elimination was a very facile step as compared to oxidative addition. Furthermore, our calculation indicated that trans-N,N‘-dimethylcyclohexane-1,2-diamine was an excellent ligand for Cu-catalyzed aryl amidation, whereas TMEDA was almost completely inactive. These theoretical results were in good agreement with experimental observations, suggesting the possibility of using a combined theoretical and experimental approach to rationally improve Cu(I)-catalyzed cross-coupling reactions.