Born in Cincinnati, John Henry Twachtman worked as a decorator of window shades, as had his father. At the same time he took night classes at the Ohio Mechanics Institute and then enrolled at the McMicken School of Design (which later became the Art Academy of Cincinnati), where Twachtman studied with Frank Duveneck. Duveneck was a recognized painter who had recently returned from Munich, and he urged Twachtman to go to Munich to attend the Royal Academy of Fine Arts. In 1875 Twachtman went to Munich, and during his European stay he accompanied Duveneck and his fellow Munich colleague, William M. Chase, on a painting trip to Venice. Returning to the United States in 1878, Twachtman exhibited with the newly formed Society of American Artists in New York; he was elected a member the following year. In 1879 Twachtman met and began a lifelong friendship with J. Alden Weir. In 1881, he made a wedding trip to Europe, joining Weir and his brother John on a painting expedition to Holland and Belgium.
Between 1883 and 1885 Twachtman studied, traveled, and worked in France, meeting other American Impressionists Childe Hassam, Willard Metcalf, and Theodore Robinson in Paris. In 1889 Twachtman began teaching at the Art Students League, and, with the profits from a cyclorama he had painted with Arthur B. Davies in Chicago, he purchased a home in Connecticut near Weir's farm.
Twachtman's naturalism combines the earth tones and the fluid brushwork of Duveneck and the Munich school, the muted harmonies and abstract patterning of Whistler, and, the atmospheric effects of Claude Monet. Writing in A Collection in the Making, Duncan Phillips noted that “Twachtman’s was perhaps the finest sensibility in American art.”
Among his many awards, Twachtman received a silver medal at the World's Columbian Exposition in Chicago in 1893, and a gold medal at the 1894 Buffalo Academy of Fine Arts annual exhibition. In 1897 he and Weir withdrew from the Society of American Artists and formed The Ten American Painters. Estranged from his family, Twachtman spent the summers of 1900 and 1901 in Gloucester, where he died suddenly on August 8, 1902.