The U.S. Material Management and Minimization Reactor Conversion Program is developing low enrichment fuel systems encased in Al-alloy for use in research and test reactors. Monolithic fuel plates have local regions where the UMo fuel plate may come into contact with the Al-alloy 6061 (AA6061) cladding. This results in the development of interdiffusion zones with complex microstructures with multiple phases. In this study, the microstructural development of diffusion couples, U7 wt%Mo, U10 wt%Mo, and U12 wt%Mo vs. AA6061, annealed at 600 °C for 24 h and at 550 °C for 1, 5, and 20 h, were analyzed by scanning electron microscopy with x-ray energy dispersive spectroscopy. The microstructural development and kinetics were compared to diffusion couples UMo vs. high purity Al and binary AlSi alloys. The diffusion couples developed complex interaction regions where phase development was influenced by the alloying additions of the AA6061.