Metallographic microscopy (OM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and room-temperature tensile, tearing, and fatigue crack extension experimental methods were used to investigate the effect of the four final cold-rolling deformations （13%、23%、46%、68%） after intermediate annealing on the grain morphology and damage resistance properties of the Al-3.9Cu-0.74Li-0.68Mg alloy sheets. The results indicate that with increasing cold-rolling reduction after intermediate annealing, complete recrystallization occurred in the sheets after solution treatment, leading to a significant reduction in the average grain size and aspect ratio, with grains tending to become more equiaxed. The primary precipitates in the aged alloy were T1 phase, and the size, number density, and volume fraction of T1 phase showed little variation among the four reduction levels. Quantitative calculations of the contributions of different strengthening mechanisms to the yield strength revealed that the strengthening of the alloys with the four reduction levels was mainly attributed to the precipitation strengthening of T1 phase, contributing 336-367 MPa to the yield strength. With increasing cold-rolling reduction, the fatigue crack growth rate of the sheets increased, resulting in deteriorated fatigue performance, while the fracture toughness showed an upward trend. Fine grains were beneficial for improving fracture toughness but detrimental to fatigue property.