In this work, a series of Cu- and/or Zn-modified alumina-supported CrOx catalysts have been synthesized by wetness impregnation method and characterized using the combined techniques, including Raman spectroscopy, UV vis DR, XRD, XRF, H-2-TPR and low-temperature N-2 sorption, to reveal the effect of the modifiers on the catalyst performance in a fixed-bed isobutane dehydrogenation into isobutylene. The Zn-based modifier is shown to decrease the reducibility of the supported chromium species and reduce the stability of the redox ones, which results in the decreased catalyst activity in isobutane dehydrogenation. The Cu-based modifier on the contrary facilitates the formation of high amount of redox chromium species that leads to the activity growth. The modification by both Cu- and Zn-based modifiers provides an enhanced catalyst performance caused by the synergistic effect of the modifiers and chromium species. The incorporation of the modifiers into alumina support facilitates the formation of the surface defective spinel phases that prevent the incorporation of chromium into the alumina surface and establish the conditions to form the high amount of the active redox chromium species.