The son of a prominent Connecticut physician, Robert B. Brandegee developed early interests in botany, ornithology, and the tight, careful drawing technique taught him by his aunt, Sarah Tuthill. Although he was educated at the Worthington Academy and the Edward L. Hart School for Boys in Farmington, it was probably only with study under Thomas Farrer and either John H. or John W. Hill that he was able to unite successfully his three interests. Farrer and the Hills, major exponents of the American Pre-Raphaelite movement, undoubtedly encouraged him to produce the minute, painstakingly descriptive watercolors of birds and flowers which characterize his art during the late 1860s. His work was seen in the first exhibition of the Society of American Painters in Water Color in 1867. Two years later, he moved to Hartford to teach his precise method of drawing.
In April 1872, Brandegee sailed for France with fellow Connecticut artists William Faxon and the brothers Charles No‰l and Montague Flagg. His European sojourn was an extended one, possibly nine and a half years. During that time, he made sketching trips throughout Europe, studied in the atelier of Louis-Marie-Fran‡ois Jacqueson de la Chevreuse and at the Ecole des Beaux-Arts in Paris, and socialized with such American friends as Julian Alden Weir, Dwight Tryon, and the Flaggs. In France, Brandegee began painting figure subjects and portraits, and his handling of the oil paint broadened considerably.
Returning to the United States, Brandegee rented a New York studio which he kept for fifteen years. However he soon moved to Farmington, and in 1881 took the position of head of the art department of Miss Porter's School for Girls. Primarily a teacher, Brandegee exhibited only rarely during his career. He was a founder and instructor at the Connecticut League of Art Students in Hartford, and was a central figure in the local artistic community.
The painter married cellist Susan Lord in 1898. Five years later, he retired from teaching. His book, From the Open Book of Nature, was published in 1901. The writing displays a continued love of birds and plants as well as an admiration for such diverse artists as Hans Holbein the Younger, Jules Bastien-Lepage, Jean Fran‡ois Millet, and Jean-Louis-Ernest Meissonier. Several years before he died, Brandegee wrote an unpublished autobiography.