Spoleto suffered in the earthquakes in  1703, 1767 and 1780. 

When Spoleto escaped the worst effects of the earthquake of 1703, Bishop Pietro Gaddi credited his prayers before what he believed to be the cranium of St Pontian in the crypt of San Ponziano.  This led to an upsurge in the cult.  The authenticity of the relic was confirmed in 1745 and again in 1805, when it was enclosed in a new silver reliquary. 

Abbot  Jerome Richard described the life of the hermits of Monteluco in 1762:” Today, there is some echo of the past.  There are twelve dwellings inhabited by individuals and their servants, who are all celibate.  When one dies, the place falls vacant and the house may not be taken without the consent of the surviving eleven.  These people are known as the hermits of Monteluco.  They are generally well-to-do gentlemen from Spoleto who choose to live a retired life and can afford to do so comfortably”.

Bishop Francesco Maria Loccatelli (1772 - 1812) was close to Pope Pius VI, who stayed in Spoleto in 1781.  It seems likely that Pius VI recommended the young architect Giuseppe Valadier, whom Bishop Loccatelli commissioned to redesign the interior of the Duomo in 1785. 

In 1796, Bishop Loccatelli received in Spoleto Cardinal Gregorio Barnaba Chiaramonti, the future Pope Pius VII when he was expelled from his see of Imola. 

Spoleto became the administrative capital of the Dipartimento del Clitunno during a short period of Roman Republic in 1798.

In 1801, Bishop Loccatelli was created a cardinal by Pius VII.  He received the pope in 1805, on his return from France.   An inscription at Villa Redenta records this stay.

After the incorporation of the Papal Staes into the Napoleonic Kingdom of Italy in 1808, most of modern Umbria fell within the newly constituted Dipartimento del Trasimeno, with its capital at Spoleto.  The anti-clerical prefect, Baron Antoine-Marie Roederer needed to encouragement to implement the decree (1810) that mandated the confiscation of ecclesiastical property and the suppression of religious orders and lay confraternities, although e conceded that Bishop Locatelli would be missed when he died in 1811.  He was forced to flee in disguise after the fall of Napoleon in 1814, although he subsequently looked back fondly on his 5 years in Spoleto and maintained a correspondence with the Spoletan engineer Pietro Fontana).

In 1831, Pompeo Campello, the president of the short-lived revolutionary council of Spoleto, hosted Louis Napoleon (the future Emperor  Napoleon III of France) in Palazzo Campello.  Pompeo's son Paolo married Marie Bonaparte, niece of Napoleon III.  In 1887, she founded the Società Operaia di Mutuo Soccorso, a society of noble women that provided financial assistance for its members during illness or in retirement, which held its meetings in the palace.

On 17th September, 1860, when the Piedmontese troops of General Filippo Brignone took the Rocca from the vastly out-numbered papal forces in the war of Italian Reunification.