In this work, the effect of Sc content on the microstructures and mechanical properties of Al-Zn-Mg-Cu-Zr alloys prepared using spray deposition was studied. Microstructure observations reveal that not only the grain size, but also the coarse secondary phase can be refined by Sc addition through the formation of a hybrid structure coupled by η-MgZn2 and Al3(Sc, Zr) phases near and at the grain boundaries. It is inferred that the primary Al3(Sc, Zr) particles can act as nucleation sites for the η-MgZn2 phase during the deposition process. With the increase of Sc content, the continuous secondary phase at the grain boundaries converts gradually into small discontinuous particles, which contributes to the considerable improvement in tensile strength and elongation. The alloy with 0.2 wt% Sc exhibits excellent combinations of ultimate tensile strength of 831±3 MPa and elongation of 10.2 ± 0.4% after T6 heat treatment, and the elongation increases by almost 50% compared to the Sc-free base alloy.