Rossetti's first edition of poems was printed in 1807 by Giovanni Avalloni, who offered to have Rossetti's poems published after hearing him recite a few passages. The volume was never reprinted and contains poems that Rossetti himself describes by saying that some of them were "poor" and none of them were "exactly good". Throughout his early career, Rossetti published poems that were "patriotic" and supported the "popular movement" in Sicily which resulted in him receiving a grant from Ferdinand I of Naples in 1820. When the king revoked the constitution in 1821, many supporters of the constitution were persecuted and forced into exile, and Rossetti then lived in Malta for three years before settling in London in 1824. He held the post of Professor of Italian at King's College London from 1831, as well as teaching Italian at King's College School, until failing eyesight led to his retirement in 1847.

Rossetti's published works include literary criticism, Romantic poetry such as his long poem Il veggente in solitudine of 1846, and his Autobiography. He is thought to be the basis of the character Pesca in Wilkie Collins' 1860 novel The Woman in White.

He married Frances Polidori, daughter of another Italian exile Gaetano Polidori, and they had four children:

• Maria Francesca Rossetti
• Dante Gabriel Rossetti
• William Michael Rossetti
• Christina Georgina Rossetti