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Dussek was one of a number of foreign-born composers, including Muzio Clementi and John Field, who contributed significantly to the development of a distinct "London" school of pianoforte composition. In part, this was due to the superior nature of piano manufacture in England. Joseph Haydn, for instance, composed his famous E-flat sonata after playing a piano of better construction and greater range lent him by Dussek

Dussek was one of the first piano virtuosos to travel widely throughout Europe, performing at courts and concert venues, and was celebrated for his technical prowess. During a nearly ten-year stay in London, he was instrumental in extending the size of the pianoforte, and was the recipient of one of John Broadwood's first 6-foot (1.8-meter) pianos.

Dussek came froma long line of professional musicians, which began in the early 1700s and continued well into the 20th century. His first musical instruction came from his father, who began teaching him piano at 5, and organ at age 9. He also sang in the church choir.

After these early studies in Bohemia, where he was reported to be a poor and lazy student he entered the services of one Captain Männer, an Austrian military man, in 1778. Dussek traveled with the Captain to Belgium in 1779, where he became the organist at the St. Rumbold's cathedral in Mechelen,where he gave his first public recital, playing his own compositions.He then travelled to the Dutch Republic, where a well-received concert in Amsterdam brought him to the royalty's attention. He was invited to The Hague, where he gave lessons to the three children of Stadtholder William V.While at the Hague he gave a performance before Kaiser Joseph II of Austria, who alaso acknowledged Dussek's prowess. By 1782, after leaving Männer's service, he was in Hamburg, where he gave a concert on the "new English fortepiano".

From Hamburg he moved to St. Petersburg, where he was a favorite of Catherine the Great. While there he was introduced to a technician named Hessel, who had developed a keyboard version of the glass harmonica, an instrument Dussek went on to master. After Dussek left St. Petersburg, he took a position as music director for Prince Antoni Radziwill in Lithuania, where he stayed about a year. His departure from Lithuania may have been prompted by an affair he was rumored to have with the Prince's wife. He toured Germany for the next few years as a virtuoso performer on the piano and on the glass harmonica,eventually arriving in Paris in 1786.

In Paris Dussek became a favorite of Marie Antoinette, who tried to dissuade him from going on a performing tour to Milan in 1788. However, she was unsuccessful, as Dussek wanted to visit his brother Franz in Milan. Dussek's trip to Milan was quite successful. He returned to Paris, where he stayed until shortly before the outbreak of the Revolution in 1789.

Dussek made London his home until 1799. By 1790 he was well established as a performer and teacher.  He had also established a relationship with pianomaker John Broadwood. n the spring of 1791, Dussek appeared in a series of concerts, a number of which featured Sophia, the young daughter of music publisher Domenico Corri. In a concert on June 15 that year, the pair played a piano duet together; they were married in September 1792. Some of the concerts in 1791 and 1792 featured both Dussek and Joseph Haydn; the older Haydn wrote quite favorably of Dussek in a letter to the latter's father following one of the 1792 concerts. The other highlights of 1792 included the beginning of a music publishing venture with Sophia's father Domenico. This business, while successful at first, fared poorly in later years, and the circumstances of its failure spurred Dussek to flee London in 1799, leaving Corri in debtor's prison.

Dussek then toured Germany, where he became one of the first "glamour" pianists. According to Louis Spohr, Dussek was the first to turn the piano sideways on the stage "so that the ladies could admire his handsome profile. Before long he took up a position with Prince Louis Ferdinand of Prussia, who treated him more as a friend and colleague than as an employee. Together, they sometimes enjoyed what were called "musical orgies." When Prince Louis Ferdinand was killed in the Battle of Saalfeld, Dussek wrote the moving Sonata in F sharp minor, Elégie harmonique, Op. 61

In 1807, despite his earlier affiliation with Marie Antoinette, Dussek returned to Paris in the employ of Talleyrand, the powerful French foreign minister.He wrote a powerful sonata (Sonata in A flat major, Op. 64, C 221) called Le Retour à Paris (The Return to Paris). This imposing sonata also received the nickname Plus Ultra in heated response to a piano sonata by Joseph Woelfl, said to be the last word in pianistic difficulties, entitled Ne Plus Ultra. The remainder of his life he spent performing, teaching and composing in Prussia and France. His personal beauty had faded and he became grossly fat, so much so that he was eventually unable to reach the piano keyboard. He also developed a fondness for strong drink which probably hastened his death.