Interactions between superconducting Bi2Sr2CaCu2O8+x films and substrates were investigated by ion backscattering, x‐ray diffraction, and four‐point probe resistivity measurements. During annealing at temperatures above‐ 800 °C, Bi2Sr2CaCu2 oxide films rapidly reacted with alumina, Si, Si covered with SiO2, and quartz, resulting in catastrophic failure. Zr‐based barrier layers were used to minimize film‐substrate interactions. When a single ZrO2 layer was interposed between the superconducting oxide film and the underlying substrate, the Bi2Sr2CaCu2 oxide films showed a large‐grained polycrystalline microstructure and exhibited the orthorhombic structure. Films on sapphire showed transitions to the superconducting state beginning near 100 K with zero resistance achieved at 70 K. Films on Si and thermally grown SiO2 showed a similar drop in resistance around 95 K, whereas the transition was broad and the zero resistance state was not reached. For films on quartz, high thermal stress caused cracking of the superconducting oxide film. Best results were achieved using a barrier composed of a Zr‐Si‐O mixed layer underneath ZrO2. In this case, the films grown on Si and quartz were uniform and showed the onset to superconductivity at 95 K, attaining zero resistance at 70 K.