Sufficient mechanical ductility of high-burnup Zircaloy-4 fuel cladding is important to prevent large-opening ruptures and significant fuel dispersal during postulated in-reactor and spent-fuel processing accidents. The effect of irradiation, oxidation, and hydriding at high fuel burnup may degrade cladding ductility to the extent that such large ruptures are possible under severe loadings. To understand this susceptibility to failure, this study focused on mechanical testing coupled with detailed finite-element modeling and analyses. Under ring-compression-type loading at room temperature, tensile cracks form within the corrosion-induced oxide layer under elastic loading. The oxide crack then propagates into the cladding wall under additional loading with little to no measurable plastic strain, as confirmed by both experiment and analyses of plastic hoop strain in the ring. For cladding with the oxide removed prior to testing at ≤1 %/s, cracking of the underlying hydride rim comprised of circumferentially oriented hydrides occurs at low plastic hoop strain (≤3 %), whereas the finite-element analysis suggests that the base alloy with a relatively small amount of hydrides appears to fail at higher strain (>8 %). At even higher strain rates (≈400 %/s), cracking within the hydride rim occurs at near-zero ductility, but the base alloy continues to remain highly ductile. These room-temperature results indicate that the hydride rim is sensitive to strain rate, whereas the base alloy is relatively not. With the precipitation of ≈100 % radially oriented hydrides, the cladding exhibits near-zero ductility at room temperature and ≈0.1 %/s. This study suggests that the ring-compression test coupled with finite-element modeling and analysis may be used to estimate crack-initiation strains in irradiated cladding materials with susceptible microstructures and under various deformation rates.