Jean Mouton was one of the most important motet composers of the French Renaissance period.

He enters the historical record when, at the age of 18 or older, he was appointed a singer and also a teacher of religious subjects in the collegiate church of Notre Dame in Nesle in 1477. In 1483 he rose to the position of maître de chapelle there. The documents showing this also say that he was a priest, so his age was a minimum of 25.

There is a gap of over 15 years in his history, when he is noted as being maitre des enfin (or director of choir boys) at Amines Cathedral, and the author or organizer of the performance of a mystery play. It is considered likely that he earned his master's degree, perhaps in Paris, after leaving his position in Paris and before arriving in Amines.

In 1501, he became director of music in the collegiate church of St André in Grenoble. King Louis XII and his wife, Queen Anne of Brittany, visited Grenoble in June 1502. It appears that they took Mouton with them, for church records show that he left his position there without the permission of his chapter, and other records soon after that show he had joined Queen Anne's chapel some time during that decade. The Queen arranged in 1509 that Mouton would be appointed a canon at St. André in Grenoble, in absentia, meaning he got the income but did not have to do the work. (Such sinecures were not uncommon during this period.)

Mouton remained attached to the royal court for the rest of his life, remaining when François I took the throne. Whether the title existed or not, he filled the functions of an official court composer. He wrote both secular and sacred music for specific public and private royal functions, including royal weddings. For instance, his motet Inter natos mulierum is though to have been written to Queen Anne's order after she was cured of an illness in 1506 and attributed the cure to a relic of John the Baptist. He wrote a touching motet, Quis debit oculis, on the Queen's death in 1514.

Another, Missus et angelus Gabriel was composed for the arrival of Louis XII's new wife, Mary Tudor, in Paris in 1514. Whatever music he wrote on the occasion of Louis' death less than a year later is unknown, but he wrote Domine salvum fac regem for the coronation of François I in Reims in 1515, and celebrated that King's first notable military victory, at the Battle of Marignano in that same year, with Exalte Regina Galliae, even though the losers in that battle were the forces of Pope Leo X. When the Pope and the King met to conclude a peace treaty in December of that same eventful year, they were accompanied by their own respective musical establishments. On hearing Father Mouton's musicians and music, the Pope rewarded him by appointing him an apostolic notary.

Leo remained fond of Mouton's music. Some sources describe him as the Pope's favorite composer, and it is likely that he sent several Masses to the Pope.

Mouton's fame was widely spread, and he was among the first composers to have an entire volume of his music published. This was done by the pioneer of music printing, Petrucci, who issued a book of his Masses in 1515. Another important collection of his music is a compilation of his motets issued in 1555, several years after his death. This attention allows a large proportion of his works to survive, numbering over 100 motets, 15 masses, and more than 20 chansons. Another legacy of his stems from his having been the teacher of Adrian Willaert, who himself became a great teacher in the Franco-Netherlands style, which exerted great influence in Italian music of the high Renaissance. On the other hand, it is unlikely that Mouton was (as has been speculated) a pupil of Josquin.

While Mouton's music uses many of the techniques associated with Josquin's, his musical personality is entirely different. Josquin's temperament was fiery, while Mouton tended to write calming, meditative music with smooth, flowing polyphony.

For the most part, the music is written in longer notes of even pace, with a few shorter notes used mainly to add variety. In his religious music he seems not to have cared much whether the accents of the music matched that of the texts, and therefore the words are not easily understood. However, in his writing for political occasions, where the words were less familiar and much more important, he did take care that the music helped project them.

The description of this music might suggest that much of it suffered sameness or that it was so uniform that it becomes dull, but this is not generally the case. Within the music is the work of a brilliant contrapuntal thinker. His Nesciens mater virgo virum is a quadruple canon partly based on a plainchant. There are distinct periods in his music that mirror the age's general progress from reliance on a cantus firmus to newer devices such a parody and paraphrase. In later motets he used a repetitive structure that seems to anticipate the Baroque's ritornello technique.

In 1518, Duke Lorenzo de Medici or Urbino married Madeleine de la Tour d'Auvergne. One of their wedding gifts was a collection called the Medici Codex, an elegant illuminated manuscript of music of the time, of which Mouton was probably editor-in-chief.

Once again, in 1520, Mouton was involved in a kind of musical contest attending a peace parley when François met King Henry VIII of England at the Field of the Cloth of Gold and both monarchs brought their musicians.

Toward the end of his life, Mouton received another beneficence, at St. Quentin, which is where he died and was buried.