He succeeded his father in Aleppo in 1146 while his brother Saif ad-Din Ghazi came to power in Mosul. Almost as soon as he began his rule, he defeated an attempt by the Crusaders to retake the County of Edessa, which had been conquered by Zengi in 1144. In 1147 the leaders of the Second Crusade, called after the fall of Edessa, decided to attack Damascus, the city that had allied with the Kingdom of Jerusalem when Zengi had attempted to conquer it. Damascus requested help from Nur ad-Din this time, however, and the Crusader siege was a failure.
After relieving the siege, Nur ad-Din attacked the Principality of Antioch in June, 1149. Raymond of Antioch was killed in the ensuing Battle of Inab, and Nur ad-Din symbolically bathed in the Mediterranean Sea.
Nur ad-Din finally gained possession of Damascus after besieging the city in 1154; Syria was now politically unified as one family was in control of the three most important cities.
However, Ascalon had fallen to the Crusaders in 1153, leaving Egypt isolated from Syria. In 1163, the Crusaders attacked Egypt, which had been politically weakened by a series of very young Fatimid caliphs. Nur ad-Din did not want to spare his own army for a defense of Egypt, but his commander Shirkuh convinced him to invade in 1164. This succeeded in driving out the Crusaders, although further Crusader invasions did not end until Egypt was taken over by Nur ad-Din in 1169. Shirkuh's nephew Saladin became sultan of the newly conquered territory.
Nur ad-Din felt Egypt and Syria should be politically and military united, although Saladin began to ignore Nur ad-Din's authority. Both were gathering armies for what seemed to be the inevitable battle, when Nur ad-Din died in 1174. Saladin would eventually come to power in both Syria and Egypt and almost completely conquer the Crusader states.