Boccherini's compositions were first published when he was 17 years old. In 1765 Boccherini and his father went to Milan, which at the time was a magnet for talented musicians. It was there that he wrote his first string quartet. In the same year, the ill health that would plague Boccherini all his life began to take its toll. The composer endured a further blow in 1766 when his father died. He formed a new partnership with the violinist Filippo Manfredi; they toured Italy in 1767 and made their way to Paris, where they became a sensation. In Paris Boccherini published a number of notable works, including a set of six string quartets. Following his successes there, Boccherini began writing and publishing prolifically.
In 1769 Boccherini and Manfredi journeyed to Spain, where the composer enjoyed great acclaim. Boccherini then took up another new genre, the string quintet. He in fact became best known for these works, written for string quartet with an additional cello. Now enjoying the benefits of a steady job, Boccherini married in 1771.
Boccherini's wife died of a stroke in 1785. That year his Spanish patron, Archbishop Don Luis, also died, leaving Boccherini without a position. He petitioned King Charles, asking to be retained in some musical position. Charles granted him a pension and assigned him various musical duties. There was an upturn in Boccherini's fortunes in 1786 when he was commissioned as "Composer of Our Chamber" by Friedrich Wilhelm, who was soon to become King of Prussia. Though he wrote most of his new music for Friedrich Wilhelm, Boccherini remained in Spain, where he wrote his only opera, a zarzuela called La clementina.
In 1787 Boccherini remarried. In 1796 he entered into an arrangement with publisher, composer, and piano manufacturer Ignaz Pleyel, who both praised and published Boccherini's works while cheating him of income. In February 1803, Boccherini was reported as living in "distress," but this is as likely from emotional depression as financial hardship, for in 1802 two of his daughters died from an epidemic within a few days of each other. In 1804 both his wife and his only living daughter died. It seems clear that Boccherini, although he continued to compose up to the end, had little interest in living, and died on May 28, 1805 of what was described as "pulmonary suffocation." He was buried in the Church of San Justo in Madrid. In 1927 his remains were disinterred and he was reburied in the Basilica of San Francesco in his hometown of Lucca.