In 1834, while composing poems inspired by paintings, Frances met Samuel Stillman Osgood, a young portrait artist at the Boston Athenaeum. He asked her to sit for a portrait. They were engaged before the portrait was finished and married on October 7, 1835.

After their marriage, the couple moved to England. On July 15, 1836, their first daughter, Ellen Frances, was born. In 1838, while in England, she published her collection of poems A Wreath of Flowers from New England which included Elfrida, a dramatic poem in five acts. She then published another volume of poetry, The Casket of Fate.

Due to her father’s death, the Osgoods returned to Boston in 1839. After the birth of their second daughter, May Vincent, on July 21, 1839, they moved to New York City. Osgood became a popular member of the New York literary society and a prolific writer. Many of her writings were published in the widely popular literary magazines of the time. She sometimes wrote under the pseudonyms “Kate Carol” or “Violet Vane”. Her book, The Poetry of Flowers and the Flowers of Poetry was published in 1841. Some of her other published works were The Snowdrop, a New Year Gift for Children (1842), Rose, Sketches in Verse (1842), Puss in Boots (1842), The Marquis of Carabas (1844) and Cries in New York (1846).

In February 1845, Poe gave a lecture in New York in which he criticized American poetry, especially that of Henry Wadsworth Longfellow. He made special mention, however, of Osgood, saying she had “a rosy future” in literature. Though she missed the lecture, she wrote to her friend, saying Poe was “called the severest critic of the day”, making his compliment that much more impressive.

It is believed Poe and Osgood first met in person when introduced by Nathaniel Parker Willis in March 1845 when Osgood had been separated from (but not divorced from) her husband. Poe’s wife, Virginia, was still alive, but in ill health. Poe may have been attracted to Osgood because they were both born in Boston and possibly due to her childlike qualities which were similar to Virginia’s. She may have already been in an early stage of tuberculosis, just like Virginia.

In 1845, Poe used his role as one-third owner of the Broadway Journal to print some of Osgood’s poems, including some flirtatious ones: “The Rivulet’s Dream” (1845), “So Let It Be. To–” (1845), “Love’s Reply” (1845), “Spring” (1845), “Slander” (1845), “Echo-Song” (1845), “To–” (1845), “A Shipwreck” (1845) and “To ‘The Lady Geraldine” (1845). Poe responded with published poems of his own, occasionally under his pseudonym of Edgar T. S. Grey. Most notable is his poem “A Valentine”. The poem is actually a riddle which conceals Osgood’s name, found by taking letter 1 from line 1, letter 2 from line 2, and so on. Despite these passionate interchanges, the relationship between Poe and Osgood is often considered purely platonic.

Fellow poet Elizabeth F. Ellet, whose affection Poe had scorned, spread rumors about Poe and Osgood’s friendship, even contacting Virginia about alleged improprieties. Ellet even suggested that Osgood’s third child, Fanny Fay, was not her husband’s, but Poe’s. Fanny Fay was born in June 1846, but died in October. Poe biographer Kenneth Silverman says the possibility of Poe as Fanny Fay’s father is “possible but most unlikely”. Osgood, in an attempt to protect her public character, sent Margaret Fuller and Anne Lynch to request Poe return her personal letters to him to be destroyed. In July 1846, Osgood’s husband, Samuel, demanded Ellet apologize to his wife, lest he sue her for defamation. Ellet responded in a letter, retracted her statements, and put the blame on Poe and his wife, Virginia. Osgood and Poe did not interact after 1847.

Osgood and her husband reconciled in 1846, and moved to Philadelphia for a short time to get away from the scandal. Although she was ill, she continued to write. She was confined to her room because of her illness by 1847, when her daughters were eleven and eight years old; much of her poetry from this period reflects her concern for them. Her husband, having difficulty making money as a painter, left her again in 1849 to join the California Gold Rush. He returned shortly before her death.

Osgood died of tuberculosis in 1850 at her home in New York. By then, she had lost her ability to speak; her last word, “angel”, was written on a slate to her husband. She was buried in her parents’ lot at Mount Auburn Cemetery in Cambridge, Massachusetts. In 1851, a collection of her writings was published by her friends and titled The Memorial, Written by Friends of the Late Mrs. Frances Sargent Locke Osgood. It was reissued as Laurel Leaves in 1854 and was edited with a biographical introduction by Griswold. The volume was meant to raise money for her memorial headstone. However, Fanny Fern noted that, by 1854, the plot remained unmarked and criticized Samuel Osgood in her book Fern Leaves from Fanny’s Port-Folio. Samuel Osgood noted in the New York Evening Post that he had already designed a monument, inspired by her poem “The Hand That Swept the Sounding Lyre”, which was soon installed.

Osgood’s two daughters died the year after their mother; May Vincent Osgood died on June 26, 1851, and Ellen Frances died August 31.