Abstract: The effect of atomic clusters in Al-Cu-Mg alloys with various aging conditions on the fatigue crack propagation behavior was investigated using transmission electron microscopy (TEM), atom probe tomography (APT), scanning electron microscopy (SEM) and fatigue testing. The results showed that there were small-sized atomic clusters (< 100 atoms) in the naturally aged samples while the larger ones (> 100 atoms) occurred in the artificially aged samples at 170 ℃. The number density of larger atomic clusters (> 100 atoms) increased gradually with the artificial aging time at 170 ℃, and S' phases began to form after aging at 170 ℃ for 8 h. The obstruction of dislocation slip by small clusters was limited. Thus, the fatigue crack mostly propagated along the slip band with a high propagation rate. The large clusters were harder to dissolve during cycle deformation, thus reducing the cyclic softening effect and enhancing the FCP resistance. The moving dislocations likely bypassed the S' phase, resulting in a lack of plane reversible slip and crack closure effects and inducing a high propagation rate. Therefore, the 170 ℃/1 h sample exhibited the best fatigue crack growth resistance due to the higher number density of large atomic clusters and the absence of the S' phase.