Nablus was subsequently founded during the Roman period when Emperor Vespasian established the city of Flavia Neapolis in 72 CE, 2 kilometers (1.2 mi) west of the ruins of Shechem.

Because of its strategic geographic position on key trade routes and the abundance of water from nearby springs, Neapolis evolved into a prominent cultural, religious, and commercial center.

In the 10th century, the Arab geographer al-Muqaddasi, described it as abundant of olive trees, with a large marketplace, a finely paved Great Mosque, houses built of stone, a stream running through the center of the city, and notable mills.

[11] Queen Melisende of Jerusalem resided in Nablus from 1150 to 1161, after she was granted control over the city in order to resolve a dispute with her son Baldwin III.

Crusaders began building Christian institutions in Nablus, including a church dedicated to the Passion and Resurrection of Jesus, and in 1170 they erected a hospice for pilgrims.

[13] Under Mamluk rule, Nablus possessed running water, many Turkish baths and exported olive oil and soap to Egypt, Syria, the Hejaz, several Mediterranean islands, and the Arabian Desert.

[15] In 1831–32 Khedivate Egypt, then led by Muhammad Ali, conquered Palestine from the Ottomans; the destruction of Acre and further increased the political importance of Nablus.

During the 1936–1939 Arab revolt in Palestine, the British authorities demolished buildings in the Old City quarter of Qaryun suspected of harboring insurgents or hiding weapons.

Habala is the largest quarter, with relatively modern buildings, and its population growth led to the development of two smaller neighborhoods: al-Arda and Tal al-Kreim.

[2] The Old City of Nablus, like many historic urban centers in Palestine, faces significant challenges, including physical deterioration of buildings, lack of infrastructure, and the effects of the Israeli occupation, which have led to damage from military incursions and restricted access.

[21] Efforts have been made to preserve its architectural heritage, such as the 1999-2003 Master Plan for the Preservation and further Development of the Historic Centre of Nablus, Palestine by the Institute of Urbanism at Graz University of Technology, instituted by the Nablus Municipality and funded by the Austrian Development Agency,[22][23] and the subsequent restoration project led by the Taawon Welfare Association.