William Holbrook Beard began his career as portrait painter. In 1856, he traveled to Italy, Germany, and Switzerland with fellow artists Albert Bierstadt and Thomas Worthington Whittredge. In 1858, Beard briefly settled in Buffalo, New York, helping to establish an art community that eventually culminated in the establishment of the Buffalo Fine Arts Academy in 1862. In 1859, Beard moved to New York City and opened a studio in the renowned Tenth Street Studio Building, specially built in 1857 to house artists. At that time, Edwin Church, William Merrit Chase, Albert Bierstadt, and Winslow Homer were fellow resident artists. Beard exhibited extensively in New York, Cincinnati, Chicago, Montreal, San Francisco, and Boston, but he reserved his best work for exhibition at the National Design Academy in New York City.

Beard became an immensely popular animal painter, and he painted a large variety of animals, favoring rabbits, cats, monkeys, squirrels, and especially bears. Both lauded and criticized for his humorous satires, he often substituted animals for humans in his visual social commentary. He represented the condition of man and universal concerns by painting allegorical and fantasy subjects. He also produced work drawn from high and low literature, depicting characteristics of jealousy, pride, drunkenness, and greed.

Beard was a member of the National Academy of Design and the Century Association. His work is recognized in many private collections and museums, including the Smithsonian American Art Museum, the Utah Museum of Fine Arts, and the National Museum of Wildlife Art.