The year 1850 brought another crucial change to Rossetti's life. He met the beautiful Elizabeth Siddal (1829-1862), the daughter of a cutler. He painted and drew "Lizzie" — as everyone knew her — obsessively. At first the poverty of their circumstances prevented their marriage, though later in the 50s Rossetti's imagination began to be invaded by other beautiful women, including Fanny Cornforth (1835?-1905) and Jane Burden (1839-1914), who would marry Rossetti's friend William Morris. Nonetheless, Rossetti's devotion to Elizabeth never really failed, though their relationship grew increasingly troubled. They married in 1860, but two years later Elizabeth died of an overdose of laudanum. Her health had been uncertain for a number of years.

Through the 1850s Rossetti worked mainly on his painting. The initial intense period of his imaginative writing all but ceased for a time in 1852. Rossetti poured himself into his art, where he seemed — to his own judgment — unable to express himself exactly as he wanted. He gave up oil painting for a time and turned to water colour, a medium in which he produced some of his greatest works.

In terms of his public career, the central event of this period was the so-called "Jovial Campaign", the 1857 project to paint the walls of the Debating Hall of the Union Society in Oxford. As it turned out, the murals were executed but almost immediately faded and disappeared because Rossetti and his friends did not understand how properly to prepare the walls for the paintings. Despite this disaster, the project attracted great attention to Rossetti and his friends — in this case, largely a new cast of friends including Edward Jones (later Burne-Jones) and William Morris.

The Jovial Campaign ought to be seen as the culminant event in the years 1856-57, when Rossetti and the PRB finally gained a position of recognized cultural authority. Two other projects of these years were also important. In 1856 William Morris and his friends launched The Oxford and Cambridge Magazine. A sequel to The Germ, and in certain obvious ways a much superior production, it too perished after a short run — this time, after a year. But the magazine brought Rossetti a new set of attachments that would prove fateful for all concerned. The other event was the publication of Moxon's illustrated edition of Tennyson's selected poetry, which finally appeared early in 1857. The book carried illustrations by various artists of the day. Rossetti's contributions, which illustrated "The Palace of Art" and several other poems, are stunning. From the point of view of his career, his appearance in this book defined him as an artist of established position.

The death of Elizabeth early in 1862 put a (temporary) end to some elaborate publishing plans that Rossetti had set in train. In 1861 he assembled the poetical translations of medieval Italian poetry that he had been doing in the 1840s. He finished the work and brought out, at the end of the year, the important volume The Early Italian Poets (later revised and reissued in 1874 as Dante and his Circle). His plan was to publish, as an accompanying volume of original poetry, a book to be called Dante at Verona and other Poems. Though advertised as forthcoming in his book of translations, Rossetti never issued the work. In one of the two most celebrated acts of his life, Rossetti buried the manuscript volume in the coffin with his wife. (The second was his recovery of the volume, in 1869, from Elizabeth's grave.)