Both his mother, who was a painter, and his father, who was a surgeon, supported Colin Campbell Cooper in his ambition to become an artist. At twenty-three he enrolled in the Pennsylvania Academy of the Fine Arts, Philadelphia, where he studied under Thomas Eakins. By 1886, after traveling in Holland, Belgium, and Brittany, Cooper was attending the Académie Julian under Henri-Lucien Doucet as well as studying in Delécluse's studio. This was the first of the artist's many foreign travels and the beginning of his interest in plein air-isme painting and the picturesque European scene.
In 1895 Cooper was again in Philadelphia, teaching watercolor painting at the Drexel Institute. The following year much of the work he had done was destroyed in the fire that burned down the Hazeltine Galleries in Philadelphia.
Cooper married the painter Emma Lampert in 1897, then returned to the Académie Julian in Paris. During the winter of 1897-98 he traveled through Spain, and before going back to Philadelphia in 1901 he visited the artists' colony in Etaples, Normandy, and traveled in the Low Countries and the chateaux region of France. In 1902 he went abroad again, this time touring the English countryside. It was after his return to New York in the same year that Cooper began a long series of panoramic views of American urban skyline, choosing his subjects primarily from New York, Chicago, and Philadelphia.
Cooper continued his extensive travels: Europe once more in 1906; India in 1913; and the American West in 1915-16, spending the winter in Los Angeles. He was surely in New York for much of 1917 to 1920, when World War I made European travel unwise; this was also the period of his term on the Academy Council.
In 1920 Cooper moved permanently to Santa Barbara, California. He became the dean of the School of Painting at the Santa Barbara School of the Arts and was active in the local art community. He helped found the Santa Barbara Art Club in 1924, while also starting a theater group, The Strollers, which performed a number of comedies he authored.
The Academy's memorial to Cooper, entered into Council minutes on April 27, 1938, noted:
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Mr. Cooper was best and very widely known for his interpretation of architectural subjects. The unique charm of individual buildings, the picturesqueness of city streets appealed to him. . . . Mr. Cooper found the same inspiration in the skyscrapers and canyon-like streets of America as in the strange thoroughfares and ancient structures of the old world.
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