Skopje archaeology has uncovered a vast prehistory in the region that perhaps dates back well before 4,000 B.C.  Settled by various bands and tribes between the Paleolithic era and ancient Greek times, Philip of Macedon fame and his son, Alexander the Great, were the first people to really put Macedonia on the map, basing attempts at world conquest from their native region.

Under Roman domination, Skopje was known as Scupi and became a heavily-latinized center of culture and commerce.  The city grew large as a regional capital of sorts, with Roman theaters and other evidence of infrastructural development being uncovered in modern archeological digs.

A relatively quick embrace of Christianity took hold of Skopje culture and art, and as a province of the Eastern Roman Empire, churches grew alongside baths and fortifications, and the city prospered until about 518, when a major earthquake undid most all these accomplishments.  
Byzantine Emperor Justinianus I was born in a village just outside Skopje, however, and his reign naturally brought resurgence to the region, as did a massive immigrant of Slavs, including a tribe called the Berziti, who are believed to have, over time, de-Latinized the capital’s name from Scupi into Skopje.

By the eleventh century, Macedonia was an independent state, though it was a brief stretch of autonomy, as the Byzantines re-conquered the region and brutalized its rebellious inhabitants.  

After exchanging rulers a couple times more, Skopje succumbed to Ottoman military might in 1392, under which domination Skopje grew even more as it was used as a launching pad for further conquests.

In 1689 the Austrians came, saw, and set fire to the town, wreaking particularly havoc upon Jewish settlers.  Still under Turkish rule, however, Skopje would not be liberated until 1944, and then only briefly before falling under the sway of Yugoslavia, only to be freed once more upon that country’s relatively recent dissolution.