The city was strategically situated near ancient trade routes, and recent excavations have unearthed fragments of pottery indicating settlement there in the early 4th millennium BCE. Known as Hamtap in the Middle Ages, the city was an important stronghold guarding the Syrian routes and was captured by Turks in 1183. Thereafter it changed hands among various Turkmen and Arab dynasties and Mongol and Timurid invaders until its final absorption into the Ottoman Empire in the early 16th century.

Called Ayıntab under the Ottomans, it was occupied by the British in 1919 and by the French until 1921. By then it had become a centre of Turkish nationalist resistance to European occupation.

Upon its return to Turkey in 1922, Mustafa Kemal (later called Atatürk), founder of the republic, renamed it in honour of its heroic stand. Well built, with stone houses, paved streets, and covered bazaars, Gaziantep is bordered by gardens, vineyards, and olive and nut groves.