Du Bellay was born into a noble family of the Loire River valley, and he studied law and the humanities in Poitiers and Paris. He published The Defence & Illustration of the French Language in 1549. In it he asserted that French is capable of producing a modern literature equal in quality and expressiveness to that of ancient Greece and Rome. He argued that French writers should look not only to Classical texts but also to contemporary Italy for literary models. In 1549–50 du Bellay published his first sonnets, inspired by the Italian poet Petrarch.

In 1553 he went with his cousin Jean du Bellay, a prominent cardinal and diplomat, on a mission to Rome. By this time Joachim du Bellay had started to write on religious themes, but his experience of court life in the Vatican seems to have disillusioned him. He turned instead to meditations on the vanished glories of ancient Rome in the Antiquités de Rome and to melancholy satire in his finest work, the Regrets (both published after his return to France in 1558).

Throughout his life du Bellay suffered ill health and intermittent deafness. His portraits show a withdrawn and austere figure and reinforce the impression of a man totally dedicated to his art. He had a sincere affection for his country and determined that it should have a literature to rival that of any other nation. He introduced new literary forms into French, with the first book of odes and the first of love sonnets in the language. Abroad, he influenced the English lyric poets of the 16th century, and some of his work was translated by Edmund Spenser in Complaints . . . (1591).