In 1955, Brodsky began writing his own poetry and producing literary translations. He circulated them in secret, and some were published by the underground journal Sintaksis (Syntaxis). By 1958 he was already well known in literary circles for his poems "The Jewish cemetery near Leningrad" and "Pilgrims”. In 1960 the young Brodsky met Anna Akhmatova, who encouraged his work, and would go on to become his mentor.  Later Anna Akhmatova laughed at the K.G.B.’s shortsightedness: “What a biography they’re fashioning for our red-haired friend!” meaning the purges and persecutions he was exposed to. In 1963, Brodsky's poetry was denounced by a Leningrad newspaper as "pornographic and anti-Soviet." His papers were confiscated, he was interrogated, twice put in a mental institution and then arrested. He was charged with social parasitism by the Soviet authorities in a trial in 1964 and sentenced to five years hard labor, of which he served 18 months on a farm in the village of Norenskaya in the Arctic Archangelsk region. Brodsky's sentence was commuted in 1965 after protests by prominent Soviet and foreign cultural figures.

On 4 June 1972 he was put by the Soviet authorities on a plane for Vienna. Although the poet was invited back after the fall of the Soviet Union, Brodsky never returned to his country. Brodsky was awarded the 1987 Nobel Prize in Literature "for an all-embracing authorship, imbued with clarity of thought and poetic intensity". The prize coincided with the first legal publication in Russia of Brodsky's poetry as an exile. He was also awarded the McArthur scholarship in 1981 and several other prizes, as well as received the National Order of the Legion of Honour.

Brodsky died of a heart attack aged 55, in his New York City apartment. He was buried on Isola di San Michele cemetery in Venice, Italy. In 1997, a plaque was placed on his house in St. Petersburg (the former Leningrad) with his portrait in relief, and the words "In this house from 1940 to 1972 lived the great Russian poet Iosif Aleksandrovich Brodsky".