MacNeil's early artistic education was accomplished at Boston's Massachusetts Normal Art School, which had been established in 1873 to train drawing teachers. In Boston in the late 1870s, he also had some contact with William Rimmer, either as a student or as an attendee at his anatomical lectures. The extent or exact nature of this study is unclear. Frank Jewett Mather recalled that "To the end of his life MacNeil mentioned Rimmer with admiration and gratitude."
Following his 1886 graduation from the Normal Art School, MacNeil taught drawing and modeling at Cornell University, Ithaca, New York, before leaving in 1888 for Paris to pursue academic training as a sculptor. He entered the Académie Julian under Henri Chapu, and studied with Jean Falguière at the Ecole des Beaux-Arts.
Returning to America in 1892, he worked with sculptor, Philip Martiny, on figures for various buildings at the Columbian Exposition in Chicago; for this work he was awarded the Designers Medal. He remained in Chicago and taught at the Art Institute school for three years. It was during this period that he became interested in depicting the American Indian, several of whom he met at the Exposition. He spent several months traveling throughout the West, making portrait and anthropological studies of Native Americans.
Shortly after his 1895 marriage to fellow-sculptor, Carol Brooks, MacNeil won the Rinehart Scholarship, established by the estate of American sculptor, William Henry Rinehart. This permitted him to pass the next four years in Rome, where he produced many of his most well-known Indian subject pieces. In 1900 he worked on decorations for the United States Government Building at the International Exposition in Paris. His The Sun Vow (Metropolitan Museum of Art, New York) won a silver medal in the Exposition; it remained one of his most popular Indian studies. The following years brought more honors for work exhibited at the 1901 Pan-American Exposition, Buffalo, New York; the 1902 Charleston (South Carolina) Exposition; the 1904 Louisiana Purchase Exposition, in Saint Louis, Missouri; the 1910 Buenos Aires (Argentina) Exposition; and the 1915 Panama-Pacific International Exposition, in San Francisco.
On his return to New York from Rome, MacNeil set up a studio at College Point, Long Island. A sequence of important commissions quickly established him as a major American sculptor. His work of 1905, The Coming of the White Man, modeled for the city of Portland, Oregon, was followed by the McKinley Memorial for Columbus, Ohio, of about 1907, and a figure of Ezra Cornell executed for the campus of Cornell University.
After World War I, major commissions included the equestrian Pony Express Rider in Saint Joseph, Missouri, the figure Washington as Commander-in-Chief of the Army for the Washington Square Arch, New York, and the pedimental group for the east wing of the United States Supreme Court Building, Washington, D. C. Many portrait figures and busts, several of which are in the collection of New York University, date from these years as well.
His design for the United States Liberty quarter was minted between 1916 and 1932.
MacNeil was a member of the Academy school faculty from 1906 into 1919. He then was visiting professor at the American Academy in Rome in 1919 and 1920, and later taught at the Pratt Institute, and the Art Students League in New York. He was president of the National Sculpture Society from 1910 to 1912 and again from 1922 to 1924, and his design, Into the Unknown, was adopted as the Society's seal.
By the late 1920s, however, MacNeil's style, basically formed in the Beaux-Arts aesthetic, was considered old-fashioned; the modern trend toward abstraction was gaining ground. His last major work, the Fort Sumter Memorial, was executed in 1932, fifteen years before his death. The wide geographical distribution of his work, especially his monumental pieces, as well as his designs for medals and coins has made his oeuvre more familiar to today's public than his name. As his student, Adolph Block, wrote: "The public . . . often enjoys a sculpture by MacNeil without being aware of the man who created it."