George Henry Smillie first studied engraving under his father in New York City. Subsequently, in 1861, he studied painting with James M. Hart. The following year he exhibited at the National Academy of Design and was elected an associate in 1864. In 1868 he exhibited at the Boston Athenaeum. He exhibited at the Boston Art Club from 1880 to 1908. He became a full member of the National Academy of Design in 1882 and was very active in the institution, acting as treasurer and recording secretary. He was also a member of the American Watercolor Society.
Smillie spent his professional life in New York City, although he made painting trips to all part of the country. He traveled to the Adirondacks in northern New York, the White Mountains of New Hampshire during the 1870s and 1880s, and the Rockies and Yosemite in 1871.
In 1881 he married Nellie Sheldon Jacobs, a pupil of his brother, James David Smillie. All three shared a studio for many years in New York City.
His works have been preserved at the Oakland Museum of Art, the Union League Club of Philadelphia, the National Academy of Design, and the Rhode Island School of Design.
Smillie died in 1921 in Bronxville, NY.