Henry Hubbell's family moved to Lawrence, Kansas, when he was four years old. In 1886, at age sixteen, he graduated from the Lawrence high school and went to Garden City, Kansas, where he probably did some theatrical scene painting. He quickly relocated to Chicago, where he painted signs and billboards. The move to Chicago probably had more to do with a desire to gain formal training in art; he began studying at the School of the Art Institute of Chicago within a year of arriving in the city. Over the next ten years he worked under various Art Institute teachers, including William Merritt Chase, Dennett Grover, and John Vanderpoel. Hubbell supported himself during this period through commercial and book illustration. In 1895 he married Nellie Rose Strong, a fellow student.
The Hubbells left for Paris in the autumn of 1898 and remained there until late summer 1904. On his arrival Hubbell studied briefly at the Académie Julian under William-Adolphe Bouguereau, Jean-Joseph Benjamin-Constant, and Jean-Paul Laurens. Almost simultaneously, he began studies with James Abbott McNeill Whistler at Whistler's Académie Carmen. In 1900 he made a private arrangement with Raphael Collin to critique his work. The award of an honorable mention in the Paris Salon of 1901 suggests Hubbell had moved beyond the level of student.
During this period Hubbell continued doing illustrations for American magazines, a welcome source of income. The Hubbells summered at various resorts, including Dieppe, Étaples, Fontainebleau, and Nanteuil-le-Houdouin, Oise, all of which supplied subjects for his brush. With Walter Shirlaw and his wife, Florence Manchester, they spent most of 1902 in Madrid, where Hubbell was chiefly occupied in the close study of Velásquez through precise copying of his masterworks in the Prado.
Hubbell served on the European jury selecting works for the art exhibition at the Louisiana Purchase Exposition in Saint Louis of 1904; this experience may have influenced his decision to return to the United States that year. However, after about a year in America-during part of which he taught at the Art Institute of Chicago-the Hubbells returned to France and spent the next five years abroad. Hubbell's career flourished in this period. His paintings were shown, given awards, and purchased both in France and America. He and his wife also traveled widely in these years, living for periods in Nice and in Venice. In 1908 they took a house in Giverny, where Hubbell knew Edmund Greacen, Frederick MacMonnies, and Richard Emil Miller.
The Hubbells finally returned to the United States in the spring of 1910. Initially they were based in Chicago, though Hubbell spent most of his time fulfilling portrait commissions in the East. In 1911 they established residence in New York and the following year acquired a summer home in Silvermine, Connecticut, which they kept until 1916. Hubbell was appointed head of the school of painting and decoration of the Carnegie Institute of Technology, Pittsburgh, Pennsylvania, in 1918, a position he held until 1922. He then was based in Springfield, Illinois, until 1924, when he moved permanently to Miami Beach, Florida. Important portrait commissions continued to flow to him, among them U.S. Secretary of the Interior Harold Ickes (1934) and, through Ickes, President Franklin D. Roosevelt (1939, Roosevelt Library, Hyde Park, New York).