Increasing the service life of critical components of aluminium alloys under cyclic loading by surface modification is an important task. In this work, the evolutions of the microstructure and mechanical properties of the aluminium alloy D16T under cyclic loading and high-frequency mechanical impact (HFMI) modification of the surface are investigated. As revealed by x-ray diffraction, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), the microstructure of the samples consisted of an aluminium matrix and precipitates of strengthening phases with different dispersion levels (2.5 vol.%). As established, severe plastic deformation during HFMI surface modification leads to a 46% increase in surface microhardness HV100 (1.46 GPa) and a 75% increase in fatigue resistance (9.2 103 cycles at σ_max = 440 MPa) of the D16T-alloy samples compared to the initial state that is associated with the formation of ultrafine grains and compressive stresses in the surface layer. The evolutions of deformation defects and microstructure are analysed at several scale levels using diffraction and microscopic methods, as well as molecular dynamics (MD) modelling. Clusters of dislocations and point defects around spherical inclusions followed by the matrix delamination along the second-phase particles’ interfacial boundaries and slip bands of different systems detected in the aluminium lattice during MD modelling of plastic deformation found their experimental confirmation at another scale level by direct TEM observation of the microstructure of the original and HFMI-modified samples after cyclic loading. According to the experimental microstructure analysis and modelling results, possible mechanisms for the formation of nucleated cracks are the accumulation of dislocations and point defects around the particles of the second phase with subsequent delamination along the interphase boundaries and the formation of slip bands, which can reach the surface during cyclic loading, and the formation of compressive stresses in the ultra-dispersed surface layer are the factors, which prevent crack propagation and premature failure. The results obtained indicate that HFMI modification of the surface using ultrasonic equipment can effectively enhance the fatigue resistance of the D16T alloy under low-cycle fatigue conditions, with maximum cyclic stresses approaching the yield point.