After moving to Jesi, near Ancona, they took on the descriptive name of Pergolesi. Their only son Giovanni Battista was born in Jesi on January 4th, 1710. Giovanni studied music in Jesi, taking violin lessons from Francesco Mondini, and showing a remarkable natural aptitude. When he was sixteen he was invited to study at the Conservatorio dei Poveri di Gesu Cristo (Conservatory of the Poor Men of Jesus Christ) in Naples.

In 1727, after Giovanni had been at the conservatory for about a year, the family suffered a serious blow when is mother died and her dowry went missing. His father suffered a loss of income, and the small family entered a very difficult period. During this time Pergolesi began composing. The first work to attract attention was his sacred drama, La Conservatione di San Guglieme d'Aquitania (1731), given its first performance by his fellow students at a Naples monastery.

Attempting to get back into the theater, Pergolesi wrote a deliberately Neapolitan flavored work Lo Frate 'Nnamorato, (libretto by G. Federico). It was first performed on September 27, 1732 and was received with great enthusiasm by the public. A year later the opera seria, Il Prigionier Superbo appeared accompanied by its comic intermezzo La Serva Padrona. The serious opera met with some success, but La Serva Padrona was to become the most famous of all intermezzi.

It became detached from its original position in support of the serious work, and went on to win international fame, particularly in Paris. In 1752, a production of La Serva Padrona provoked a pamphlet war between the partisans of French and Italian opera (the "Guerre des Bouffons" or "War of the Bouffons") and led to the founding of French opera comique. To this day La Serva Padrona has enjoyed an audience of its own.

These two years of success were culminated with Pergolesi’s entering the service of Marzio IV Carafa, Duke of Maddaloni in 1734. Giovanni traveled to Rome with his new master in 1734 where he enjoyed the privilege of having his Mass in F performed.

By now Pergolesi was aware of something seriously wrong with his health, and his remaining time was spent attempting to put his affairs in order. Years of fast and reckless living had weakened his resistance to infection, and he was now in the grip of consumption.

The Duke of Maddalon allowed him to become a house guest of the monks of the brotherhood of San Luigi di Palazzo at their Franciscan monastery in Pozzuoli in the early months of 1736. Pergolesi left Naples having instructed his aunt to take possession of any property he left behind; he clearly did not expected to return to Naples. He died in Pozzuoli on March 16th, 1736 at the age of 26.

After Pergolesi’s death, his setting of Stabat Mater, a Latin poem attributed to Jacopone da Todi, was quickly recognized as something out of the ordinary and achieved an international reputation.

La Serva Padrona in Paris precipitated the "Guerre de Bouffons", the name given to one of the most remarkable episodes in operatic history, when all of Paris was divided from 1752 to 1754 between the supporters of traditional French serious opera as exemplified by Lully and Rameau, and those of the new Italian opera buffa as exemplified by Pergolesi’s La Serva Padrona.