Born in Bolton le Moors, Lancashire, in 1801, Cole emigrated with his family to the United States in 1818, settling in Steubenville, Ohio. At the age of 22, Cole moved to Philadelphia and later, in 1825, to Catskill, New York, where he lived with his wife and children until 1848.
Cole found work early on as an engraver. He was largely self-taught as a painter, relying on books and by studying the work of other artists. In 1822, Cole started working as a portrait painter and later on, gradually shifted his focus to landscape.
In New York, Cole sold five paintings to George W. Bruen, who financed a summer trip to the Hudson Valley where the artist produced landscapes featuring the Catskill Mountain House, the famous Kaaterskill Falls, the ruins of Fort Putnam, and two views of Cold Spring. Returning to New York, he displayed five landscapes in the window of William Colman's bookstore; according to the New York Evening Post the two views of Cold Spring were purchased by Mr. A. Seton, who lent them to the American Academy of the Fine Arts annual exhibition in 1826. This garnered Cole the attention of John Trumbull, Asher B. Durand, and William Dunlap. Among the paintings was a landscape called View of Fort Ticonderoga from Gelyna. Trumbull was especially impressed with the work of the young artist and sought him out, bought one of his paintings, and put him into contact with a number of his wealthy friends including Robert Gilmor of Baltimore and Daniel Wadsworth of Hartford, who became important patrons of the artist.
Cole was primarily a painter of landscapes, but he also painted allegorical works. The most famous of these are the five-part series, The Course of Empire, which depict the same landscape over generations—from a near state of nature to consummation of empire, and then decline and desolation—now in the collection of the New York Historical Society and the four-part The Voyage of Life. There are two versions of the latter, one at the National Gallery in Washington, D.C., the other at the Munson-Williams-Proctor Arts Institute in Utica, New York. Among Cole's other famous works are The Oxbow (1836), The Notch of the White Mountains, Daniel Boone at his cabin at the Great Osage Lake, and Lake with Dead Trees (1825) which is at the Allen Memorial Art Museum. He also painted The Garden of Eden (1828), with lavish detail of Adam and Eve living amid waterfalls, vivid plants, and deer. In 2014, friezes painted by Cole on the walls of his home, which had been decorated over, were discovered.
Cole influenced his artistic peers, especially Asher B. Durand and Frederic Edwin Church, who studied with Cole from 1844 to 1846. Cole spent the years 1829 to 1832 and 1841 to 1842 abroad, mainly in England and Italy.