Durand was apprenticed to an engraver from 1812 to 1817, later entering into a partnership the owner of the firm, who asked him to run the firm's New York branch. He engraved Declaration of Independence for John Trumbull in 1823, which established Durand's reputation as one of the country's finest engravers. Durand helped organize the New York Drawing Association in 1825, which would become the National Academy of Design; he would serve the organization as president from 1845 to 1861.
His interest shifted from engraving to oil painting around 1830 with the encouragement of his patron, Luman Reed. In 1837, he accompanied his friend Thomas Cole on a sketching expedition to Schroon Lake in the Adirondacks and soon after he began to concentrate on landscape painting. He spent summers sketching in the Catskills, Adirondacks, and the White Mountains of New Hampshire, making hundreds of drawings and oil sketches that were later incorporated into finished academy pieces which helped to define the Hudson River School.
Durand is particularly remembered for his detailed portrayals of trees, rocks, and foliage. He was an advocate for drawing directly from nature with as much realism as possible. Durand wrote, "Let [the artist] scrupulously accept whatever [nature] presents him until he shall, in a degree, have become intimate with her infinity...never let him profane her sacredness by a willful departure from truth."
Like other Hudson River School artists, Durand also believed that nature was an ineffable manifestation of God. He expressed this sentiment and his general views on art in his "Letters on Landscape Painting" in The Crayon, a mid-19th century New York art periodical. Wrote Durand, "[T]he true province of Landscape Art is the representation of the work of God in the visible creation..."
Durand is noted for his 1849 painting Kindred Spirits which shows fellow Hudson River School artist Thomas Cole and poet William Cullen Bryant in a Catskills landscape. This was painted as a tribute to Cole upon his death in 1848. The painting, donated by Bryant's daughter Julia to the New York Public Library in 1904, was sold by the library through Sotheby's at an auction in May 2005 to Alice Walton for a purported $35 million. The sale was conducted as a sealed, first bid auction, so the actual sales price is not known. At $35 million, however, it would be a record price paid for an American painting at the time.
In 2007, the Brooklyn Museum exhibited nearly sixty of Durand's works in the first monographic exhibition devoted to the painter in more than thirty-five years. The show, entitled "Kindred Spirits: Asher B. Durand and the American Landscape," was on view from March 30 to July 29, 2007.