The effects of various rolling reductions (64.7%, 72.1%, 81.4% and 88.2%) on the microstructures and mechanical behaviors of Sc-containing Al-3.2Cu-1.5Li-based alloys were experimentally investigated through XRD, SEM (equipped with EBSD), TEM and the tensile test. The results showed that the grains of hot-rolled and T6-treated alloys are mainly dominated by substructure features, and the addition of the trace Sc element can obviously impede the static and dynamic recrystallization due to the formation of fine and stable nano-Al3(Sc, Zr) particles. Additionally, the combined effects of fine grains, dispersion, substructure and precipitation strengthening make the alloys with a rolling reduction of 81.4% possess higher tensile properties. With an increase in the rolling reduction, the tensile strength of the alloys increases first and then decreases, while the elongation gradually increases and then reaches a plateau, which was ascribed to the variation in the grain size and substructure features.