The sign of the exchange interaction in dinuclear CrIIINiII complexes was analyzed using theoretical methods based on density functional theory. This approach allowed us to reproduce the experimental J values correctly. In addition, the Kahn–Briat model, which uses the square of the sum of the overlaps between the magnetic orbitals to correlate with the exchange coupling constant, provided a reasonable correlation between the different types of CrIIINiII complexes when using biorthogonalized orbitals. We also examined the exchange interactions in two polynuclear CrIIINiII complexes: a Cr7Ni ring and an S-shaped Cr12Ni3 complex. We concluded that both systems exhibit antiferromagentic interactions, and that the CrIII⋅⋅⋅NiII interactions are similar in value to the CrIII⋅⋅⋅CrIII exchange couplings.