Single-Event Burnout (SEB) can cause hard damage to devices, leading to permanent failure. However, previous studies have rarely explored the effects of high-energy proton irradiation-induced SEB in β-Ga2O3 Schottky Barrier Diode (SBD), and the underlying mechanisms remain largely unexplored. Experimental results indicate that the reverse bias voltage during irradiation is a critical factor influencing the failure of β-Ga2O3 SBD. Compared to 300 MeV proton irradiation without bias, the introduction of a 300 V reverse bias voltage results in a significant reduction in forward current density (JF). When the reverse bias voltage reaches 400 V or higher, the 300 MeV proton induces SEB in the device. The SEM image of the damaged region reveals that the irradiated device has “voids” formed due to the melting of the Ga2O3 material. Geant 4 and TCAD simulation results indicate that the burnout phenomenon is caused by the elevated lattice temperature inside the device, which results from the implantation of secondary particles under a high reverse bias voltage. As the reverse bias voltage increases, the maximum lattice temperature of β-Ga2O3 SBD also rises. When the reverse bias voltage is sufficiently high, the local lattice temperature inside the device reaches the melting point of Ga2O3 material, ultimately leading to SEB.