At the time of Charlemagne, the town came under the temporal and religious power of the bishops of Vercelli, from which it was freed by Frederick Barbarossa, Holy Roman Emperor and King of Italy.

In 1745, following the defeat of the Piedmontese army at the Battle of Bassignano during the War of the Austrian Succession, Casale was occupied by the victorious French and Spanish troops.

[6] The vast limestone deposits in the hills nearby caused, in the late 19th and early 20th centuries, several concrete factories to open up in the town.

[8] From 1907 to 1986, Casale was the site of a large Eternit factory, that produced the homonymous asbestos cement, whose operations resulted in a massive environmental disaster, linked to the death of some 1,800 people from mesothelioma and other asbestos-related diseases in the area: in spite of former Eternit owner Stephan Schmidheiny and his associate, Jean-Louis de Cartie, being convicted and ordered to pay tens of millions of euros in compensation by the Turin Appeal Court in 2012, the Italian Supreme Court in 2014 declared that the statute of limitations had expired in the case.

[10] Named for Giuseppe Mazzini, a key republican figure of the Risorgimento, it is dominated by an 1843 equestrian statue by Abbondio Sangiorgio of King Charles Albert of Piedmont-Sardinia, dressed in Roman costume, specifically as a senator, with his knees uncovered.

A little to the east of the square is the Lombard Romanesque cathedral of Sant'Evasio, founded in 742, rebuilt in the early 12th century and consecrated on 7 January 1107 by Pope Paschal II.

The interior houses the relics of Saint Evasius and, near the presbytery, fragments of 11th-century pavement mosaics with Biblical scenes (now remounted on the walls of the corridor from the apse to the sacristy).

In 1471, after William VIII, Marquess of Montferrat had chosen Casale as the permanent location of the marquisate court, construction began of the church of San Domenico, to the north of Piazza Mazzini.

Work on the building ceased for some time, as a result of political instability; in the early 16th century a fine, if slightly incongruous, Renaissance portal was imposed on the late Gothic façade.

Also in Via Lanza is the 17th-century church of San Giuseppe, probably designed by Sebastiano Guala; a painting attributed to the Ursuline nun Lucrina Fetti (c.1614–1651,[11] brother of Domenico) shows Christ venerated by Sant’Evasio and includes a very accurate depiction of contemporary Casale with its civic tower.

The high open tower which is a landmark of Via Lanza belongs to Palazzo Morelli di Popolo; it has been attributed to Bernardo Vittone, and also to Magnocavalli—both are believed to have had a hand in the refurbishment of the building.

This brick tower, square in plan and 60 metres high, dates from the 11th century but suffered severe fire damage in April 1504 when a festival to celebrate the peace between Holy Roman Emperor Maximillian I and King Louis XII of France got out of hand.

Adorning both the walls and the vault are 15 tondi depicting prophets, apostles and the Virgin painted by Pietro Francesco Guala in 1757, the last year of his life.

The south side of Piazza Santo Stefano, facing back towards Via Saffi, is formed by the neo-classical Palazzo Ricci di Cereseto.

The imposing façade, marked by four massive brick columns, was built in 1806 to an earlier design by the local architect Francesco Ottavio Magnocavalli.

Piazza Castello is a large irregularly shaped open space used as a car park and as a market square; it is dominated by the castle of the Paleologi which occupies most of its western side.

A masterwork of Giovanni Battista Scapitta, completed after his death by Giacomo Zanetti, it is marked by an elliptical cupola, and a façade curvilinear both in plan and elevation.

The theatre, which stands at the north-eastern corner of the piazza at the end of Via Saffi, opened in 1791 with a performance of the La moglie capricciosa, an opera buffa by Vincenzo Fabrizi.

The horseshoe-shaped auditorium with stalls, four tiers of boxes and a gallery (or loggione, i.e. the gods) is richly decorated with frescoes, stucco, gilding and velvet.

The curtains of the royal box hang from a structure supported on stucco caryatids by Abbondio Sangiorgio who also designed the equestrian statue in Piazza Mazzini.

Behind the shops on the west side of Via Roma, which runs southwards from Piazza Mazzini, lay the ghetto which persisted until the emancipation of the Jews in Piedmont following Charles Albert's concession of a constitution, the Statuto Albertino, under the revolutionary pressures of 1848.

The Monumento alla difesa di Casale (Francesco Porzio, 1897; pictured right), situated to the north of the castle, commemorates the vigorous action which took place during the First Italian War of Independence in 1849 to defend the city against Austrian troops who had just taken part in the defeat of the Piedmontese army.

The historic centre is marked by many palazzi which are often Baroque in appearance (though the substance is often earlier), reflecting the urban renewal which took place in the early decades of the 18th century.

[14] The cathedral there has in its archives polyphonic music by Jean Mouton, Andreas de Silva, and Francesco Cellavenia, as well as important prints by Giovanni Pierluigi da Palestrina and other major composers of the period.

In the 17th and 18th centuries, Casale was the site for premieres of operas by Giulio Cesare Monteverdi, Pietro Guglielmi, and Pasquale Anfossi, and was the birthplace of the Swiss-Italian composer Carlo Evasio Soliva.

Junior Libertas Pallacanestro Casale Monferrato, was founded in 1956 and today competes in Lega Basket Serie A, the first tier of the sport in Italy.