The son of a Boston caterer, Willaim McGregor Paxton grew up in Boston, his family having returned from Baltimore in 1870 after a failed business venture. In 1887, Paxton won a scholarship to Cowles Art School, where he studied under Dennis Bunker Miller. He was in Paris from 1889-1893, with Bunker's past master, Jean-Leon G‚r"me at the Acad‚mie Julian and the Ecole des Beaux-Arts. He also studied with Jules Joseph Lefebvre and Jean Joseph Benjamin-Constant.
After contracting typhoid fever, Paxton returned to Boston, establishing a studio, while resuming classes at Cowles, under Joseph DeCamp. In 1894, Paxton met Edmund Charles Tarbell and Frank Benson, who were to become lifelong friends, when he joined the Art Students' Association (renamed the Copley Society in 1901). Although he supported himself by commercial illustration during this period, Paxton began establishing his reputation as a portraitist in the tradition of Ingres, for whom he had great admiration.
The artist's second visit to Europe occurred in 1897 or 1898. He married Elizabeth Okie, another Cowles student, in 1899, the year after his return. In 1901, the couple traveled to Europe. They summered at East Gloucester in 1902, the first of many summers spent at various New England coastal resorts that also included Provincetown, Hyannis and Nantucket. By 1904, when a studio fire destroyed one hundred canvases, Paxton had become a critical and financial success.
Paxton was appointed instructor of drawing from the antique at the school of the Boston Museum of Fine Arts in 1906, a position he held until 1913, when re resigned in protest of a planned reorganization. Paxton is considered a younger member of the Boston School style, a group centered around his friends Tarbell, DeCamp and Benson. Although Paxton returned to Italy during the summer of 1910, by 1911, he purchased a studio in Provincetown.
Throughout his career, Paxton served on the juries of many arts institutions and exhibitions, including the Pennsylvania Academy Annual, the 1915 Panama-Pacific Exposition, the Art Institute of Chicago, the National Academy of Design, The Corcoran Gallery of Art, while he was also the recipient of numerous awards and prizes, with his work entering prominent collections. In 1914, he was a founding member of the Guild of Boston Artists.
In 1921, the artist was in Europe during part of the summer, while in 1925 he visited Cuba. In 1933, he returned to Europe. Although Paxton suffered a stroke in 1939, he regained his health and continued painting. He died at home two years later.
