The site of the ancient Segontia ('dominating over the valley') of the Celtiberian Arevaci, now called Villavieja ('old town'), is half a league distant from the present Sigüenza. Livy mentions the town in his discussion of the wars of Cato the Elder with the Celtiberians.

The city fell under Roman, Visigothic, Moorish and Castilian rule.

Around 1123 it was taken by Bernard of Agen, its first bishop. Sigüenza played a large part in the civil wars of the thirteenth and fourteenth centuries. The fortress palace of the bishops, originally an earlier Moorish qasbah, was captured in 1297 by the partisans of the Infantes de la Cerda, and in 1355 it was the prison of Blanche of Bourbon, consort of Peter of Castile. In 1465 Diego López of Madrid, having usurped the miter, fortified himself there.

The last bishop-lord, known as the "mason-bishop", built a neighborhood below the level of the old town in a Neo-Classical style, before renouncing to the temporal lordship.

During the Spanish Civil War, the Francoist Civil Guard fortified the upper castle, while the Republican forces took to the lower cathedral.

After the war, the city limits have increased with the incorporation of 28 pedanías (villages).

The Castle of the Bishops of Sigüenza (Castillo de los Obispos de Sigüenza) is located in Sigüenza in the Province of Guadalajara in central Spain. With foundations dating back to the 5th century, it was extended by the Moors and retaken for the Christians by Bernard of Agen in 1123.

The origins of the fortifications in Sigüenza go back to the Celtiberians who inhabited the right bank of the river in the final centuries B.C. The Visigoths built a small castle in the 5th century above the town. The Moors built a large fortified castle or alcazaba in the early 8th century to defend the area against the Christian kings of Leon and Castile. It was enclosed by a defensive wall providing an area known as the medina. In 1124, the castle was retaken by Bernard of Agen allowing Simón Girón de Cisneros to build an episcopal palace there. In 1298, the castle was taken by the troops of Alfonso de la Cerda during the battle against Ferdinand IV of Castile, the boy king, but was defended by the bishop's vassals. In the 15th century, the castle was strengthened by the bishops to protect it from attacks from Aragon and Navarre.

In the late 18th century, Bishop Juan Díaz de la Guerra changed the appearance of the castle from a fortress into an episcopal palace with additional windows, balconies and stables. However, in 1808 during the War of Spanish Independence the castle was taken by the French who seriously damaged it and looted all its riches before it was recaptured by El Empecinado. The episcopal palace was further devastated by fire in the 1830s and had to be abandoned.

The cathedral is a large Gothic edifice of ashlar stone, though the lower levels show that it was built onto an earlier Romanesque cathedral. Its façade has three doors, with a railed court in front. At the sides rise two square towers, 164 feet high, built at different times, with merlons topped with large balls; these towers are connected by a balustrade which crowns the facade, the work of Bishop Herrera in the eighteenth century. The interior is divided into a nave and two aisles, in Gothic style.

The main choir begins in the transept with a Renaissance altar built by order of Bishop Mateo de Burgos. In the transept is the Chapel of Saint Liberata (Librada), the female patron saint of the city, with a reredos and the relics of the saint, all constructed at the expense of Bishop Fadrique of Portugal, who is buried there.

What is now the Chapel of St. Catherine was dedicated to St. Thomas of Canterbury by the English Bishop Jocelin. The chapel houses the sepulchre of Martín Vázquez de Arce (Martin Vasques de Arze in the spelling of the time). Vázquez died in 1486 during the conquest of Granada and his brother Fernando, bishop of the Canary Islands, ordered a portrait in alabaster where he lies on his side while reading, in one of the finest examples of Spanish funerary art. It contrasts with the recumbent figures of his parents in the same chapel.

The authors of the Spanish Generation of 1898 (Ortega y Gasset) drew attention to this statue naming him el doncel de Sigüenza, 'the doncel (royal page) of Sigüenza', but Vázquez left a widow and children. Cardinal Mendoza is interred in the main choir. Beyond the choir proper, which is situated in the centre, there is the altar of Nuestra Señora la Mayor, in black marble from Calatorao and red marble, featuring spiral Solomonic columns.

The main sacristy is also named as "of the heads". It was designed in 1532 by Alonso de Covarrubias and built by Francisco de Baeza and Martín de Vandoma. The portal is Renaissance, Plateresque, of 1573, in stone, the nut tree door has also Plateresque carvings and was damaged by a cat door and the Napoleonic troops. The half cannon vault features 304 big heads, all different, and 2000 smaller ones, hence the nickname of the room.

The cathedral's ceiling and stained glass were damaged in the Spanish Civil War, with the reconstruction ending in 1947.