A monolithic fuel design based on U–Mo alloy has been selected as the fuel type for conversion of United States’ high-performance research reactors (USHPRRs) from highly enriched uranium (HEU) to low-enriched uranium (LEU). In this fuel design, a thin layer of zirconium is used to eliminate the direct interaction between the U–Mo fuel meat and the aluminum-alloy cladding during irradiation. The co-rolling process used to bond the Zr barrier layer to the U–Mo foil during fabrication alters the microstructure of both the U–10Mo fuel meat and the U–Mo/Zr interface. This work studied the effects of post-rolling annealing treatment on the microstructure of the co-rolled U–Mo fuel meat and the U–Mo/Zr interaction layer. The U–Mo/Zr interaction-layer thickness increased with the annealing temperature with an Arrhenius constant for growth of 184kJ/mole, consistent with a previous diffusion-couple study. The phases in the U–Mo/Zr interaction layer produced by co-rolling, however, differ from those reported in the previous diffusion-couple study.