Thermal runaway (TR) is a critical and catastrophic consequence of lithium-ion battery (LIB) failure. In-situ monitoring of internal critical states during TR is essential for revealing failure mechanisms and supporting early warning. Here, we use high-speed synchrotron X-ray radiography, alongside temperature, voltage, and pressure probes on a 5.2 Ah prismatic LiNi0.5Mn0.3Co0.2O2 (NMC532) LIB under heating-induced thermal failure to characterize the internal structural damage and propagation. Complementary to physical test, a thermal runaway numerical COMOSOL Multiphysics model is developed to quantify the battery’s internal thermal behaviour. Differential scanning calorimetry (DSC) and accelerated rate calorimetry (ARC) are employed for model thermophysical parameter identification associated with the dominant exothermic decomposition reactions responsible for self-heating, as well as for model validation. This combined X-ray radiography and TR modelling technique is demonstrated as a comprehensive approach to visualizing the structural evolution of the battery’s jelly roll (JR) and effective internal thermal mapping the LIB.