Today it is a battlefield, overrun by Islamist militants controlling northern Mali who have been razing its world-heritage religious sites in a destructive rampage that the UN cultural agency has deplored as "tragic".
"Not a single mausoleum will remain in Timbuktu, Allah doesn't like it," Abou Dardar, a leader of the armed Ansar Dine group which is behind the latest wave of destruction, bluntly told AFP on Sunday.
Nicknamed "the City of 333 Saints" or "The Pearl of the Desert", Timbuktu sits just north of the Niger river and about 1,000 kilometers (600 miles) north of Mali's capital Bamako.
Listed as a UNESCO world heritage site in 1998, it has long been a tourist magnet for its magnificent mud-built mosques and shrines.
But the pickaxes and shovels being wielded again by militants from Ansar Dine (Defenders of the Faith) against what they consider idolatrous shrines are wiping out the heritage of the city founded between the fifth and 11th centuries by Tuareg desert nomads.
Ansar Dine, which follows the hardline Wahhabi strain of Islam, began destroying the cultural treasures in July believing them to be "haram" or forbidden.
The International Criminal Court warned that the vandalism was a war crime, but the Islamists followed up with more damage in October, when they smashed several Muslim saints' tombs.
In the chaotic aftermath of a March coup in Bamako, Ansar Dine planted their ominous black flags around the city as rebel groups also including Al-Qaeda in the Islamic Maghreb and the Movement for Oneness and Jihad in West Africa (MUJAO) seized the key cities in northern Mali.
Timbutku's heyday as an ancient trading hub, intellectual center and cosmopolitan crossroads in the desert is now gone as women are forced to wear veils and people flouting strict Islamic laws face brutal whippings.
After its founding, Timbuktu became a meeting point between north, south and west Africa and a melting pot of black Africans, Berber, Arab and Tuareg desert nomads.
The trade of gold, salt, ivory and books made it the richest region in west Africa and it attracted scholars, engineers and architects from across the continent, growing into a major center of Islamic culture by the 14th century.
The legend of Timbuktu began in 1324, when the Emperor of the Mali empire Mansa Mussa (1307-1332) made a pilgrimage to Mecca via Cairo with 60,000 porters, each carrying three kilograms of pure gold which he said came from Timbuktu.
This amount of gold put Timbuktu on the map as a mysterious African city of gold.
Timbuktu grew to become a metaphor for remoteness, with the saying "from here to Timbuktu" evoking images of a place so distant many do not know whether it really exists.
Upon his return, Mussa built the famous Mosque of Djingareyber, one of the city's three great mosques, still standing 700 years on.
From the jewel of the ancient Malian Empire (1230-1600), which once spanned most of western Africa, Timbuktu fell back into Tuareg hands and later formed part of the Songhai Empire, one of the world's largest Islamic empires.
Intellectual activity flourished and hundreds of thousands of ancient manuscripts remain as testament to sub-Saharan Africa's golden age covering mathematics, chemistry, physics, astronomy, medicine history and geography.
These riches, the remaining architecture and the legend had made Timbuktu one of the main draws for visitors to Mali despite its decline since 1591, when the Moroccan army plundered the city, burned libraries and killed scholars.
Many explorers unsuccessfully tried to reach Timbuktu, including Scottish doctor Mungo Park, who disappeared while sailing the Niger river alone in 1805 after his entire expedition team died along the way.
About two decades later, the Geographical Society of Paris was said to have offered a reward to the first European to visit Timbuktu and live to tell the tale.
Modern Timbuktu is an impoverished town sinking into the desert where youth unemployment is high.