Abstract: The formation mechanism of calcium vanadate and manganese vanadate and the difference between calcium and manganese in the reaction with vanadium are basic issues in the calcification roasting and manganese roasting process with vanadium slag. In this work, CaO–V₂O₅ and MnO₂–V₂O₅ diffusion couples were prepared and roasted for different time periods to illustrate and compare the diffusion reaction mechanisms. Then, the changes in the diffusion product and diffusion coefficient were investigated and calculated based on scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) analysis. Results show that with the extension of the roasting time, the diffusion reaction gradually proceeds among the CaO–V₂O₅ and MnO₂–V₂O₅ diffusion couples. The regional boundaries of calcium and vanadium are easily identifiable for the CaO–V₂O₅ diffusion couple. Meanwhile, for the MnO₂–V₂O₅ diffusion couple, MnO₂ gradually decomposes to form Mn₂O₃, and vanadium diffuses into the interior of Mn₂O₃. Only a part of vanadium combines with manganese to form the diffusion production layer. CaV₂O₆ and MnV₂O₆ are the interfacial reaction products of the CaO–V₂O₅ and MnO₂–V₂O₅ diffusion couples, respectively, whose thicknesses are 39.85 and 32.13 μm when roasted for 16 h. After 16 h, both diffusion couples reach the reaction equilibrium due to the limitation of diffusion. The diffusion coefficient of the CaO–V₂O₅ diffusion couple is higher than that of the MnO₂–V₂O₅ diffusion couple for the same roasting time, and the diffusion reaction between vanadium and calcium is easier than that between vanadium and manganese.