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Leiden was formed on an artificial hill (today called the Burcht van Leiden) at the confluence of the rivers Oude and Nieuwe Rijn (Old and New Rhine). In the oldest reference to this, from circa 860, the settlement was called Leithon. The name is said to be from Germanic leitha- "canal".

Leiden has in the past erroneously been associated with the Roman outpost Lugdunum Batavorum. This particular castellum was thought to be located at the Burcht of Leiden, and the city's name was thought to be derived of the Latin name Lugdunum. However the castellum was in fact closer to the town of Katwijk, whereas the Roman settlement near modern-day Leiden was called Matilo.

The landlord of Leiden, situated in a stronghold on the hill (motte), was initially subject to the Bishop of Utrecht but around 1100 the burgraves became subject to the county of Holland. This county got its name in 1101 from a domain near the stronghold: Holtland or Holland.

Leiden was sacked in 1047 by Emperor Henry III. Early 13th century, Ada, Countess of Holland took refuge here when she was fighting in a civil war against her uncle, William I, Count of Holland. He besieged the stronghold and captured Ada.

Leiden received city rights in 1266. In 1389, its population had grown to about 4,000 persons.

A university city since 1575, Leiden houses Leiden University, the oldest university of the Netherlands, and Leiden University Medical Center. Leiden is a city with a rich cultural heritage, not only in science, but also in the arts. One of the world's most famous painters, Rembrandt, was born and educated in Leiden. Other famous Leiden painters include Lucas van Leyden, Jan van Goyen and Jan van Steen. The city has been one of Europe's most prominent scientific centres for more than four centuries. Modern scientific medical research and teaching started in the early 18th century in Leiden with Boerhaave. Many important scientific discoveries have been made here, giving rise to Leiden's motto: 'City of Discoveries'.

Leiden University is one of Europe's top universities, it boasts thirteen Nobel Prize winners, it is a member of the League of European Research Universities and positioned highly in all international academic rankings. It is twinned with Oxford, the location of the United Kingdom's oldest university. Leiden University and Leiden University of Applied Sciences (Leidse Hogeschool) together have around 35,000 students. Leiden is a typical university city, university buildings are scattered throughout the city and the many students from all over the world give the city a bustling, vivid and international atmosphere.