Christina Rossetti was born in Charlotte Street (now 105 Hallam Street), London, to Gabriele Rossetti, a poet and a political exile from Vasto, Abruzzo, and Frances Polidori, the sister of Lord Byron's friend and physician, John William Polidori. She had two brothers and a sister: Dante Gabriel became an influential artist and poet, and William Michael and Maria both became writers. Christina, the youngest, was a lively child. She dictated her first story to her mother before she had learned to write.
Rossetti was educated at home by her mother and father, who had her study religious works, classics, fairy tales and novels. Rossetti delighted in the works of Keats, Scott, Ann Radcliffe and Matthew Lewis. The influence of the work of Dante Alighieri, Petrarch and other Italian writers filled the home and would have a deep impact on Rossetti's later writing. Their home was open to visiting Italian scholars, artists and revolutionaries. The family homes in Bloomsbury at 38 and later 50 Charlotte Street were within easy reach of Madam Tussauds, London Zoo and the newly opened Regent's Park, which she visited regularly; in contrast to her parents, Rossetti was very much a London child, and, it seems, a happy one.
In the 1840s, her family faced severe financial difficulties due to the deterioration of her father's physical and mental health. In 1843, he was diagnosed with persistent bronchitis, possibly tuberculosis, and faced losing his sight. He gave up his teaching post at King's College and though he lived another 11 years, he suffered from depression and was never physically well again. Rossetti's mother began teaching to keep the family out of poverty and Maria became a live-in governess, a prospect that Christina Rossetti dreaded. At this time her brother William was working for the Excise Office and Gabriel was at art school, leaving Christina's life at home to become one of increasing isolation. When she was 14, Rossetti suffered a nervous breakdown and left school. Bouts of depression and related illness followed. During this period she, her mother, and her sister became deeply interested in the Anglo-Catholic movement that developed in the Church of England. Religious devotion came to play a major role in Rossetti's life.
In her late teens, Rossetti became engaged to the painter James Collinson, the first of three suitors. He was, like her brothers Dante and William, one of the founding members of the avant-garde artistic group, the Pre-Raphaelite Brotherhood (founded 1848). The engagement was broken in 1850 when he reverted to Catholicism. Later she became involved with the linguist Charles Cayley, but declined to marry him, also for religious reasons. The third offer came from the painter John Brett, whom she likewise refused.
Rossetti sat for several of Dante Gabriel Rossetti's most famous paintings. In 1848, she was the model for the Virgin Mary in his first completed oil painting, The Girlhood of Mary Virgin, which was the first work to be inscribed with the initials "PRB", later revealed to signify the Pre-Raphaelite Brotherhood. The following year she modelled for his depiction of the Annunciation, Ecce Ancilla Domini. A line from her poem "Who shall deliver me?" inspired the famous painting by Fernand Khnopff called I lock my door upon myself. In 1849 she became seriously ill again, suffering from depression and sometime around 1857 had a major religious crisis.