This chapter explores the history and archaeology of Antioch in Late Antiquity, analysing the city’s evolution from its Seleucid foundation to its prominence as a Roman, Byzantine and early Islamic centre. A key argument is that Antioch’s transformation was a story not of decline but of adaptation, shaped by political shifts, natural disasters and evolving architectural traditions. This study highlights the challenges faced by early excavations, particularly the Princeton University-led campaign in the 1930s, which struggled with sedimentation, modern urban encroachment and a focus on decorative mosaics rather than structural remains. Despite these setbacks, that project yielded significant insights into Antioch’s topography, including the layout of its colonnaded streets, fora and fortifications. The chapter also examines the role of imperial patronage in reshaping the city, with figures like Constantine, Theodosius and Justinian commissioning extensive rebuilding efforts, including churches, palaces and defensive walls. While earthquakes, Persian invasions and environmental challenges altered the urban fabric, Antioch retained its status as a major intellectual, religious and economic hub well into the early Islamic period.