Predator–prey interactions may be linked to different temporal or spatial patterns, including dynamics in prey populations. Therefore, understanding the adaptive capacity and how top predators respond to shifts in prey abundance and availability is crucial for their conservation. In this study, we investigated the diet pattern of the endangered Eastern Imperial Eagle facing long-term and large-scale changes. We studied the abundance variation of its profitable prey, sousliks, and how it reflected on eagle population trajectories in a regional and temporal context. We found a significant diet alteration expressed in large decrease of brown hare (β2 = −0.83), poultry (β2 = −0.81), gulls (β2 = −0.71), and water birds (β2 = −0.57), and an obvious increase of northern white-breasted hedgehog (β2 = 0.61) and doves (β2 = 0.60). Raptors and owls raised their participation (β2 = 0.44), but white stork and different reptiles supplied more biomass. Abundance of European souslik decreased through the studied periods (adjusted R2 = 0.25, p < 0.001) which accounted for the lower proportion of this prey in the eagle’s diet. Nevertheless, the eagle population successfully adapted and significantly increased (β2 = 0.97) in most of the distribution area. The trophic strategy used by this top predator related to opportunistic foraging represents an ecological advantage that allows the species to adapt to different habitats and guarantees its future. The observed prolonged diet alteration could result in a significant negative attitude among different groups such as hunters, pigeon fanciers, and poultry keepers towards eagles. Therefore, enhanced communication with key stakeholders is needed. Conservation efforts should be focused also on the preservation of the species’ main foraging habitats and the restoration of damaged ones so as to maintain the good conditions of both primary food source and subsequent prey.