The catalytic activity of ferrite-containing catalysts with spinel structures was studied with respect to the isomerization and oxidative dehydrogenation of butenes. The total acidity of the surface of the catalysts was determined. A comparison of Mg, Zn, and Ni ferrite-containing systems showed that the catalytic activity in the isomerization of butene-1 to butene-2 increased at higher total acidities of the surface. Catalytic activity in the oxidative dehydrogenation of butene-2 decreased as the total acidity increased. A mechanism of the process was suggested to explain the lowest activity of the Mg-containing catalyst in comparison with the activities of the Zn and Ni ferrite-containing systems in the oxidative dehydrogenation of butene.