A reactivity-initiated accident (RIA)-simulated test CN-1 on a high-burnup 64 GWd/t mixed-oxide fuel rod sheathed with M5™ cladding was conducted at the Nuclear Safety Research Reactor, resulting in fuel failure. A small opening with slight ballooning deformation characterized the post-test visual appearance of the test fuel rod. Simulation using fuel performance codes FEMAXI-8/RANNS predicted rod survival under early phase loading induced by pellet-cladding mechanical interaction and subsequent boiling transition, and the cladding-surface temperature measured online confirmed the occurrence of boiling transition. The experimental observation and simulation indicate that the failure was caused by a high-temperature rupture following increased rod-internal pressure. The RANNS sensitivity analysis revealed that a mechanical state parameter dedicated to predicting plastic instability might be an effective index for evaluating the risk of rupture failure during RIAs.