Regulating the chemical/thermal stability and catalytic activity of coordination polymers (CPs) to achieve high catalytic performance is topical and challenging. The CPs are competent in promoting oxidative cross-coupling, yet they have not received substantial attention. Here, the ligand effect of the secondary ligand of CPs for oxidative cross-coupling reactions was investigated. Specifically, four new isostructural CPs [Co(Fbtx)1.5(4-R-1,2-BDC)]n (denoted as Co-CP-R, Fbtx = 1,4-bis(1,2,4-triazole-1-ylmethyl)-2,3,5,6-tetrafluorobenzene, 4-R-1,2-BDC = 4-R-1,2-benzenedicarboxylate, R = F, Cl, Br, CF3) were prepared. It was found that in the reactions of oxidative amination of benzoxazoles with secondary amines and the oxidative coupling of styrenes with benzaldehydes, both the chemical and thermal stabilities of the four Co-CPs with the R group followed the trend of -CF3 > -Br > -Cl > -F. Density functional theory (DFT) calculations suggested that the difference in reactivity may be ascribed to the effect of substituent groups on the electron transition energy of the cobalt(II) center of these Co-CPs. These findings highlight the secondary ligand effect in regulating the stability and catalytic performance of coordination networks.