Louise Chandler was educated from 1854 to 1855 at Emma Willard's Troy (New York) Female Seminary. In 1854 she published This, That, and the Other, a popular collection of verses and sketches earlier contributed to various periodicals. In 1855 she married William U. Moulton, publisher of True Flag, in which some of her poems had appeared, and she soon established herself as a literary and social force in Boston. Her verses, stories, and sketches became regular features of Godey's Lady's Book, Atlantic Monthly, Scribner's, Youth's Companion, Harper's Bazaar, and other popular magazines.

Moulton's Friday salon was frequented by such figures as Ralph Waldo Emerson, James Russell Lowell, Henry Wadsworth Longfellow, John Greenleaf Whittier, and Oliver Wendell Holmes. Moulton was Boston literary correspondent for the New York Tribune (1870–76) and book critic for the Boston Sunday Herald (1887–91). From a first trip to London in 1876, on which she made the acquaintance of many literary figures, Moulton spent increasing amounts of time there until she had virtually divided her year between London and Boston. In London her salon was prominent in the social-literary life of the city, and her personal friendships with numerous late Romantic and Pre-Raphaelite poets eased their introduction to an American readership.

Among Moulton's books are a collection of bedtime stories for children, Lazy Tours in Spain and Elsewhere (1896), and the posthumous Poems and Sonnets of Louise Chandler Moulton (1909), which collects many of the poems that were highly praised for their elegance, sensitivity, and lyricism. She also edited several volumes, including The Collected Poems of Philip Bourke Marston (1893) and Arthur O'Shaughnessy, His Life and His Work, with Selections from His Poems (1894).