One of America's best-known and revered illustrators, especially for children's books and magazines, he was born into a Philadelphia Quaker family. His father, Stephen Parrish, was a successful landscape painter and etcher.

Maxfield studied in France, England, at Haverford College, the Pennsylvania Academy of the Fine Arts, and at Drexel Institute where his teacher was illustrator Howard Pyle, who would become a major influence. He was also much admiring of Edwin Austin Abbey and artist members of the N.C. Wyeth family.

Because of typhoid fever early in his career, he had to spend much time away from the East Coast, so he traveled to the Adirondacks where it was so cold he had to discontinue the use of water-based ink for oil paint. He also went to Arizona where the landscape influenced the high coloration and distinctive style of his future work.

In 1895, he moved permanently to New Hampshire. Most of his early career he did cover designs for "Collier's" magazine. Later he turned to murals and one of his mural, considered one of the great "tour de forces" of American art was commissioned in the 1920s by Cyrus Curtis, owner of "The Saturday Evening Post" for the publication's headquarters in Philadelphia. It was a fairy tale landscape with 100,000 pieces of Tiffany glass in 260 colors held in place by thousands of wires connected to the wall. It was made in artist estates of Louis Comfort Tiffany.

At age 64, Parrish began painting romantic figures in fantastical landscapes, and a favorite model in his romantic figure work was Kitty Owen, granddaughter of William Jennings Bryan. He first visited Arizona in 1902 while working on a commission for "Century" magazine, and in the 1930s, he painted in the Castle Hot Springs area.