Worthington Whittredge had no formal artistic training. "[I] can scarcely say that I ever took lessons of any one," he stated in a letter to the Academy. His first experiences with paint were during his apprenticeship in his brother-in-law's house and sign painting firm in Cincinnati. During the late 1830s and early 1840s, the young Whittredge began experimenting with portrait and then landscape painting and, by 1846, he was confident enough to send a landscape to the Academy's annual exhibition where it was praised by no less a figure than Asher B. Durand. The following year, Whittredge began selling paintings to the American Art Union.
Despite these encouragements, Whittredge seems to have realized his inadequacies and, therefore, went to Europe in 1849 to pursue a more academic course of study. He eventually made his way to Dusseldorf where he spent several years as a pupil of Andreas Achenbach and became close friends with Emanuel Leutze, Albert Bierstadt, and other American artists. He then lived in Rome for five years and traveled extensively throughout Europe and to England.
On his return to America in 1859, Whittredge became an active participant in the New York art scene. He took a space at the Tenth Street Studio Building and became a regular contributor to the annual exhibitions of the Academy. He soon adopted the customary schedule of spending summers in the Catskills and in New England, sketching and preparing for the studio-based winters during which major oils were produced. He was an avid joiner and maintained memberships in organizations such as the Union League Club, the Lotos Club, and the Century Association. Not the least of these to benefit from his energy was the National Academy where, during the 1860s and 1870s, he served as corresponding secretary, vice-president, and, briefly, as president.
In 1866, he was a part of the General John Pope expedition to the American west where he was especially impressed by the Mississippi River and the Rocky Mountains. He made a second trip to the area in 1870 with Sanford Gifford and John Kensett. In 1880, Whittredge and his family moved to Summit, New Jersey, where he lived and worked for the rest of his life.