Coupons of fuselage skin made from the aluminium alloy D16AT (the Russian equivalent of 2024-Ò4) were obtained from several Russian TU-154 passenger aircraft after different numbers of flight cycles and different lengths of operation. The coupons were subjected to electrochemical, microstructural, and mechanical testing with the aim of identifying any trends indicating fatigue damage accumulation and residual fatigue lifetime reduction during service. Alongside this investigation, laboratory fatigue test specimens were machined from the same alloy and subjected to cyclic fatigue loading to simulate the service conditions for the coupons. Electrochemical testing was used in order to determine the evolution of the corrosion potential of the near-surface layers. X-ray diffraction analysis was also carried out to characterize residual stress and texture evolution, while microstructural investigations were made using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and secondary ion mass spectroscopy. The suitability of using electrochemical, microscopic, and diffraction characterization methods for the detection of surface structural state modification and its connection with the mechanical performance of this alloy are discussed.