Inhabited since the Prehistory Ages, evidenced by the archeological traces excavated in the area, Caltanisetta was a Greek settlement known with the name of Nissa (changed into Qalat-an-Nissa by the Arabs, Calatenixet and finally Caltanixettun under the Normans). In 212 b.C., at the end of the Second Punic War, the city, like the whole island of Sicily, was dominated by the Romans. At the decline of the Roman Empire, the city was occupied by the Arabs and the Normans till 1407, when the seignory was assigned to the Moncada Family of Paternò, that ruled till the feudal constitution was abolished in Sicily in 1812.

Important artistic and architectonic treasures are located in the nearby, such as: the excavations of Sabucina (at 12 km East of the city) where traces evidence the evolution of a village of huts (XII century b.C.) into a native settlement (VI century b.C.) and the construction of fortified walls of the V and IV centuries b.C.

The site of Gibil-Gabib (at 6 km South of the city) preserves, instead, the ruins of an antique Sicana civilization with its necropolis.

Originally founded during the Arab domination as a fortress to guard over the Salso valley, the Castle of Pietrarossa (red stone) collapsed, on Feb 27th 1567, under a landslide. The castle took its name from the colour of the dark red stones that upholstered the walls.

The Cathedral of Santa Maria La Nova, edified in late XVI century, preserves, inside, frescos of the Flemish artist Guglielmo Borremans (1720). The separation between paintings and plasters offer a theatre style look. The wooden statue of san Michele (1615) is a masterpiece of the Sicilian artist Stefano Li Volsi. In the choir area, there is a precious golden plate wooden organ completed in 1601.

The abbey of Santo Spirito, consecrated in 1153, was built under Ruggero I (XI century) in Romanesque style with three typical Norman apses, connected to each other by archways and plaster strips. The interior features a wooden Cross of the '400 and a Romanesque Baptismal font, decorated with stylized palms.

The Church of Santa Maria degli Angeli, known also as "La Vetere", rises next to the Castle of Pietrarossa. Built during the Norman dominion, it was consecrated in 1100, but has not been used for cult purposes since it was transformed into a hospital in 1873 to recover the local people from the plague of cholera.

The Church of Sant'Agata al Collegio ('600), features a wonderful façade of tuff stone and red plaster and inside preserves a marble altar entitled to Sant' Ignazio, artwork of the artist Ignazio Marabitti.

The Church of San Domenico ('400), built by the Moncada Family, features a convex outline in the central part and a concave one from the sides. The church hosts a precious painting of the artist Paladini, a portrait of the Madonna del Rosario, surrounded by the children of the Earl Francesco Moncada.

The Fountain entitled to Triton, sculptured in 1956 on the cast of the artist Michele Tripiciano, is located at the centre of the city's main square. The bronze sculpture features a horse captured by Triton and surrounded by two large sea monsters.