Using Mechanical Activation it is possible to obtain small grain size and good homogeneity in a ceramic piece. For ZnO varistor devices Mechanical Activation appears to be a good fabrication technique, since good homogeneity and small grain sizes are advantageous microstructural features. The typical formulation is composed by ZnO, Bi2O3, Sb2O3, CoO, MnO2 and Cr2O3 as raw materials, and during sintering, several dissolutions and reactions to form pyrochlore and spinel phases occur. When Mechanical Activation is applied to the entire formulation, it is difficult to know what processes are being mechanically activated due to the complexity of the system. The aim of the present work was to clarify how the mechanical activation is taking place in a typical ZnO varistor formulation. The methodology consisted in the formation of all possible combinations of two out of the five oxides above mentioned and to apply mechanical activation on the mixture of each pair of powders. The results showed that systems containing Bi2O3 are prone to react during mechanical activation. Also, reduction reactions were observed in MnO2. In addition, the powder mixture corresponding to the whole formulation was milled in a planetary mill, pressed and sintered, and varistor devices were fabricated. Improvement in the nonlinearity coefficient and breakdown voltage was observed.