The chemical interactions between the YBa2Cu3O7−x high Tc superconductor and various substrates (Si, Al2O3, ZrO2, SrTiO3, MgO, Ag, Cu, and Nb) were studied. Powders of the orthorhombic YBa2Cu3O7−x (123) phase and each of the various substrates were mixed, pressed into pellets, and subjected to either one of the following heat treatments in flowing oxygen: 600 °C for 11 h, 800 °C for 10 h, 945 °C for 5 h, and 945 °C for 17 h. The reacted samples were characterized by qualitative and quantitative x-ray diffraction, scanning electron microscopy with EDAX, electrical resistivity, and magnetic susceptibility measurements. For all substrates studied, the extent of reaction is much more significant at 945 °C than at 800 °C and 600 °C. The reaction products, in general, are some Ba compounds, CuO (and Cu2O), and the Y2BaCuO5 (211) phase. The reaction with Si results in a morphology of layers of 123/211/Ba2SiO4/CuO/Si. Reactions with Al2O3 and ZrO2 result in similar products and morphologies. Reaction with SrTiO3 results in the replacement of Ba by Sr and the formation of a Ba–Ti–Y–Cu unknown phase. With MgO, the chemical reaction results in the enrichment of MgO with Cu and the formation of an apparently glassy Ba–Cu phase. With the metallic substrates Ag, Cu, and Nb, Ag shows no interaction at all, Cu results in the formation of CuO (and Cu2O), whereas the Nb samples completely disintegrated. By comparing the percentage of remaining 123 phase in samples reacted at 945 ° for 17 h, a reactivity scale in decreasing order was obtained as Nb > Si > ZrO2 Al2O3 > SrTiO3 > MgO Cu > Ag. It is suggested that the chemical reactivity of the Y–Ba–Cu oxide superconductor is mostly controlled by the highly electropositive Ba2+ ions.