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Structural analyses of dry casks containing high-burnup fuel require cladding mechanical properties and failure limits to assess fuel behavior. Pre-storage drying-transfer operations and early stage storage subject cladding to higher temperatures and much higher pressure-induced tensile hoop stresses relative to in-reactor operation and pool storage. Under these conditions, radial hydrides may precipitate during slow cooling and provide an additional embrittlement mechanism as the cladding temperature decreases below the ductile-to-brittle transition temperature (DBTT). A test procedure was developed to simulate the effects of drying-storage temperature histories. Following drying-storage simulation, samples were subjected to ring-compression test (RCT) loading, which was used as a ductility screening test and to simulate pinch-type loading that may occur during cask transport. RCT samples with 50% wall cracking were assessed as brittle. Prior to testing high-burnup cladding, many tests were conducted with pre-hydrided Zircaloy-4 (Zry-4) and ZIRLO™ to determine target 400 °C hoop stresses for high-burnup rodlets. Zry-4 cladding segments, from a 67-GWd/MTU fuel rod, with 520–620 wppm hydrogen and ZIRLO™ cladding segments from a 70-GWd/MTU fuel rod, with 350–650 wppm hydrogen were defueled and tested. Following drying-storage simulation, the extent of radial-hydride precipitation was characterized by the radial-hydride continuity factor. It was found that the DBTT was dependent on: cladding material, irradiation conditions, and drying-storage histories (stress at maximum temperature). High-burnup ZIRLO™ exhibited higher susceptible to radial-hydride formation and embrittlement than high-burnup Zry-4. It was also observed that uniformly pre-hydrided, non-irradiated cladding was not a good surrogate for high-burnup cladding because of the high density of circumferential hydrides across the wall and the high metal-matrix ductility for pre-hydrided cladding.