Athens – Istanbul is the route followed quite by chance, by the hero of the film, a mature man, who after his recent divorce from his wife of many years and on the verge of depression, sets off on a journey in his car without a real purpose. Initially his final destination appears to be Thessaloniki, on the pretext of visiting his sick father. But quite unexpectedly, however, events on the National Road force him to play a key role in an adventure, which will culminate, after many stops and detours, in Istanbul.