Grain size is industrially important for improving mechanical properties and formability. In order to investigate the effect of grain size on the hot workability and deformation mechanisms, Al-Zn-Mg-Cu alloys with different initial grain sizes, 241.2, 100.4 and 48.4 μm, were subjected to hot compression tests. Using the established constitutive equation, the rheological behavior is described and the influence of the initial grain on the thermal deformation behavior is analyzed. Electron back-scatter diffraction (EBSD) analysis was used to study the dynamic recrystallization (DRX) mechanisms of Al-Zn-Mg-Cu alloys with different initial grain sizes. The microstructures obtained under various deformation conditions were analyzed. The results show that decreasing the initial grain size enhances both the peak stress and the activation energy for thermal deformation. Meanwhile, the dynamic recrystallization mechanism varies depending on the initial grain size. Continuous dynamic recrystallization (CDRX) is the primary DRX nucleation mode for coarse-grained alloys. Nonetheless, discontinuous dynamic recrystallization (DDRX) is predominant for alloys with fine grains.