Jommelli was born in Aversa near Naples. He studied music in Naples with Francesco Feo at the Conservatorio de' poveri di Gesu' Cristo and Francesco Mancini and Leonardo Leo at the Conservatorio della pietà dei Turchini. His first opera, L'errore amoroso was produced in Naples in 1737 under a pseudonym, and was a great success. This and other early works such as Ricimero rè dei Goti (1740) made him famous througout Italy. He lived and worked first in Venice and then in Rome where he met Giovanni Battista Martini.
He subsequently visited Vienna before taking a post as kapellmeister to the Duke of Württemburg in Stuttgart in 1753. This period saw some of his greatest successes and the composition of what are regarded as some of his best works. He returned to Naples in 1768, by which time opera buffa was more popular than Jommelli's opera seria, and his last works were not so well received. He suffered a stroke in 1771 which partially paralysed him, but continued to work until his death three years later. He died in Naples.
Jommelli wrote cantatas, oratorios and other sacred works, but by far the most important part of his output was his operas, particularly his opere serie of which he composed around sixty examples, several with libretti by Metastasio. In his work, he tended to concentrate more on the story and drama of the opera than on flashy techinical displays by the singers, as was the norm in Italian opera at that time. He wrote more ensemble numbers and choruses, and, influenced by French opera composers such as Jean-Philippe Rameau, he introduced ballets into his work. He used the orchestra (particularly the wind instruments) in a much more prominent way to illustrate the goings-on of the story, and wrote passages for the orchestra alone rather than having it purely as support for the singers. From Johann Adolph Hasse, he learnt to write recitatives accompanied by the orchestra, rather than just by a harpsichord. His reforms are sometimes regarded as equal in importance to Christoph Willibald Gluck's.