High-performance concrete (HPC) is vulnerable to spalling under high temperature conditions and it has been found that the heating rate can exert a tremendous effect on spalling of HPC. To prevent HPC from spalling, the heating rate effect should be understood. However, quantitative analyses are still lacking and the heating rate effect has not been well interpreted so far. In this paper, a numerical analysis of the heating rate effect on spalling of HPC is presented. Based on the experimental results reported in the literature, the spalling behavior of cubic HPC specimens under fire heating and slow heating with a heating rate of 5 °C/min is modeled. With a meso-level thermo-chemo-hydro-mechanical analysis, the temperature gradient induced thermal stress and the mechanical effect of build-up vapor pressure are investigated. The results show that, at different heating rates, the spalling mechanisms are different. Finally, possible manners and mechanisms of spalling are discussed.