Painter, architect, and furniture designer, William Penhallow Henderson was born in 1877 in Medford, Massachusetts. His father, William Oliver Henderson was a friend of painter William Edward Norton and an amateur painter himself. During Henderson's childhood, the family moved several times, settling in Turkey Creek, Texas, in 1879, and Clifton, Kansas, in 1886.
Returning to Boston in 1891, Henderson studied at the Massachusetts Normal Art School and, and in 1899, entered the School of the Boston Museum of Fine Arts, studying under Edmund C. Tarbell. In the following year, he won the Paige Traveling Scholarship for two years of study in Europe. His travels, from 1902-1903, included London, where he became acquainted with the family of John Singer Sargent. He also traveled to Paris, Berlin, Dresden, Madrid, and the Azores.
From 1904 to 1910, Henderson taught at the Academy of Fine Arts in Chicago. In 1904 he painted in Mexico and Arizona with colleague Carl N. Werntz. He married the poet-editor of Poetry magazine, Alice Corbin in 1905, and their only child, Alice Oliver Henderson, was born in 1907.
Between 1906 and 1907 Henderson completed ten murals for the Joliet Township High School. Mrs. Henderson's book Anderson's Best Fairy Tales, illustrated by her husband, provided the funds for a second trip to Europe from 1910-1911. In 1914, Henderson built a house and studio of his own design at Lake Bluff, Illinois, and in the same year he was commissioned by Frank Lloyd Wright to design murals for Midway Gardens, Chicago. Unfortunately, the murals were painted over shortly after completion. In the following year, he designed the scenery and costumes for the Chicago Fine Arts Theatre production of Alice in Wonderland.
Due to his wife's failing health, the family moved to Santa Fe, New Mexico in 1916, and in 1918, Henderson was employed by the U. S. Shipping Board Emergency Fleet Corporation in San Francisco to paint camouflage onto the hulls of ships during World War I.
In 1925, Henderson, with his first son-in-law John Evans, formed the Pueblo-Spanish Building Company, through which he designed and built many private homes and some public buildings, including the Railroad Ticket Office in Santa Fe. Henderson was also successful at designing carved wooden furniture. In the mid-1930s, he was appointed to the Federal Arts Project, for which he completed easel paintings and six murals for the Santa Fe Federal Court Building.
In 1937, Henderson completed the impressive Navajo House of Religion, built in the style of an American Indian hogan and later re-named the Museum of Navajo Ceremonial Art.
William Penhallow Henderson died in 1943 in Tesuque, New Mexico.