The two separated when Annie refused to marry Hunt. It's when he turned to Fanny Waugh, whose family had been friends with the painter for 15 years. Fanny took over the role of muse when the two got together. The portrait of Fanny Holman Hunt was part of a sorrowful period for the artist. William married Fanny in 1866, and eight months later, in August of the same year, they decided to move to Palestine. Hunt wanted to visit the Holy Land to use as inspiration and setting for his works. However, they were held in Marseille due to an outbreak of malaria. As they waited, Hunt set up shop in Florence to keep working. Fanny gave birth to a boy in October of that year then died two months later from a bout of cholera. Hunt had not finished his wife's portrait when she died. He had to use his memory and a photograph to complete the painting.

Fanny's portrait stays true to Hunt's style, which involved putting single figures of women in an enclosed space. He did this to bring out the physical and psychological essence of the subject. In the portrait, Fanny is standing behind a green leather chair, leaning on it in a way that hides her pregnancy. She is positioned near the fireplace where a Chinese porcelain vase and glass bowl sit on the mantle. A beautiful mirror frame is hanging on the wall. Fanny is wearing a regal purple dress, a cameo brooch and an Indian shawl around her. A bonnet hangs loosely from her hands.

Hunt insisted on having the right props for the background of this portrait. He wanted to paint Fanny wearing her favourite peacock shawl and even sent for it in Marseille. He was hoping to give the painting a personal significance. However, they didn't find the original shawl, so the painter opted for the Indian one instead. The portrait is considered a memorial of the painter to his wife. The portrait of Fanny Holman Hunt is in the Pre-Raphaelite style that Hunt helped pioneer. Currently, the painting sits at the Toledo Museum of Art.