The self-heating and high-power microwave (HPM) effects that can cause device heating are serious reliability issues for gallium nitride (GaN) high-electron-mobility transistors (HEMT), but the specific mechanisms are disparate. The different impacts of the two effects on enhancement-mode p-gate AlGaN/GaN HEMT are first investigated in this paper by simulation and experimental verification. The simulation models are calibrated with previously reported work in electrical characteristics. By simulation, the distributions of lattice temperature, energy band, current density, electric field strength, and carrier mobility within the device are plotted to facilitate understanding of the two distinguishing mechanisms. The results show that the upward trend in temperature, the distribution of hot spots, and the thermal mechanism are the main distinctions. The effect of HPM leads to breakdown and unrecoverable thermal damage in the source and drain areas below the gate, while self-heating can only cause heat accumulation in the drain area. This is an important reference for future research on HEMT damage location prediction technology and reliability enhancement.