Ditters began his career as a violin virtuoso. Employed in a church orchestra at age 10 or 11, he moved on to the court orchestra of the Prince of Sachsen-Hildburghausen. There he studied composition under Giuseppe Bonno, the court composer and Kapellmeister. He also met Gluck, a fellow violinist, and Haydn. In 1761, at age 21, Ditters was appointed court violinist. Two years later, in 1763, he made his first trip abroad, traveling to Italy with Gluck and performing.
Ditters left the imperial court in 1764 after a dispute. He became Kapellmeister for the court of the Bishop of Grosswardein, in what is now Romania, and produced mostly sacred music for five years. After a dispute with Empress Maria Theresia, the Bishop disbanded his chapel, leaving Ditters unemployed. The following year, Ditters became acquainted with the Prince-Bishop of Breslau, Schaffgotsch, who appointed Ditters court composer in 1770. The court was located in the small hamlet of Johannisberg, and to persuade Ditters to remain in such an out-of-the-way locale, the prince bestowed upon him many honors and titles, including the Order of the Golden Spur and the position of Overseer of Forests and Chief Magistrate. In 1772 Ditters gained noble status and appended "von Dittersdorf" to his surname.
During his years in Johannisberg, Ditters composed numerous symphonies, chamber works, and operas. This period is considered his most creative, and for a time he was in the running to succeed Gassmann as Kapellmeister at the court of Emperor Joseph II. In the middle 1780s, several of his compositions were performed in prestigious circumstances. The imperial palace was the venue for performances of six of his 12 "Ovid" symphonies. As a symphonist Ditters gained a reputation for humor and formal inventiveness, and even today those adventurous musicians who unearth his works are likely to be delighted by those same qualities.
The year 1786 proved to be a defining one for Ditters: his comic opera, Der Apotheker und der Doktor (The Pharmacist and the Doctor) premiered in Vienna with overwhelming success. It soon became the most popular opera in Europe, rapidly spreading to opera houses across the continent. Riding on a wave of popularity, Ditters composed eight more comic operas over the next five years, and these singspiele, works with spoken dialogue and folkish elements, proved extremely influential over the next half century. Among their direct successors was Mozart's Die Zauberflöte.
In the middle 1790s, Ditters' employment with the Prince-Bishop Schaffgotsch came to an end. History is obscure about why, but the separation was caused either by the Prince's death or by court intrigues that led to Ditters' expulsion. Ditters' popularity began fading as well. Facing an impoverished future, Ditters found another patron in Baron Ignaz von Stillfried, who in 1795 installed the composer in his castle in southern Bohemia. His final years were spent editing his works and writing his autobiographical Lebenbeschreibung (Leipzig, 1801).