The C–O homolytic bond dissociation enthalpies (BDEs) were evaluated by composite high-level G4 and 14 density function theory (DFT) methods. By comparing these DFT methods, the wB97 provided the most accurate results and the root mean square error (RMSE) is 7.6 kJ mol⁻¹ for C–O BDE calculations. Therefore, alkenyl and aryl C(sp²)–O cleavage and the substituent effect of carboxylates/carbamates were investigated by a wB97 method. Based on the mechanism of the Ni-catalyzed Suzuki–Miyaura cross-coupling reactions, the aryl C(sp²)–O BDEs and the substituent effect of Ni complexes of carboxylates/carbamates formed in the oxidative addition step were also discussed. In addition, the NBO analysis further disclosed the essence of the substituent effects on C–O BDEs.