Fully reversed tension–compression fatigue of a hybrid material comprising polymer matrix composite (PMC) co-cured with a ceramic matrix composite (CMC) was investigated. The PMC portion had a polyimide matrix reinforced with 15 plies of carbon fibers woven in an eight-harness satin weave (8HSW). The CMC portion had three plies of a quartz-fiber 8HSW fabric in a zirconia-based ceramic matrix. The hybrid PMC/CMC was developed for use in aerospace thermal protection systems (TPS). Hence, the experimental setup aimed to simulate the TPS service environment—the CMC side was kept at 329 °C, whereas the PMC side was open to laboratory air. Compression stress–strain response was studied, and compressive properties were measured at room and elevated temperature. Tension–compression fatigue tests were conducted at elevated temperature at 1.0 Hz. The evolution of tensile and compressive strains with fatigue cycles, as well as changes in the stress–strain hysteresis behavior and stiffness were examined. The tension–compression fatigue of a PMC with the same constituents and fiber architecture as the PMC portion of the PMC/CMC was studied for comparison. Tension–compression fatigue was found to be more damaging than tension–tension fatigue for both materials. The PMC outperformed the PMC/CMC in tension–compression fatigue. Post-test examination showed widespread delamination and striking non-uniform deformation modes of the PMC/CMC.