Twachtman was born of German immigrant parents on 4 August 1853 in Cincinnati, Ohio. As a boy, he decorated window shades in the factory where his father was also employed. From 1868 to 1871, Twachtman was enrolled in the evening school at the Ohio Mechanics Institute, Cincinnati; then studied for four years at the McMicken School of Design. In 1874 he established ties with Frank Duveneck, a family friend, who had returned from Munich, and was invited to paint in the studio Duveneck was sharing with Henry Farny and Frank Dengler. When Duveneck returned to Europe the next year, Twachtman and Farny accompanied him. Twachtman enrolled at the Royal Academy of Fine Arts, Munich, where he studied with Ludwig von Loefftz for two years; he also worked at Polling, the popular village for American artists, situated in the Bavarian Alps. In 1877, Twachtman joined Duveneck and William Merritt Chase in Venice, but he returned to Cincinnati in 1878 upon learning of the death of his father.

He exhibited at the first exhibition of the Society of American Artists in 1878 and became a member of the Tile Club. In autumn 1880, Twachtman returned to Europe, where he joined the staff of Duveneck's school in Florence, Italy. When the school closed, Twachtman returned to Cincinnati and in 1881 married Martha Scudder, the daughter of a prominent local physician. The two went on a wedding trip to Europe where Twachtman met Anton Mauve and became familiar with the work of Jules Bastien-Lepage. The couple returned to Cincinnati, where their son was born. Twachtman was back in Europe from 1883-1885, where he studied with Clarence Rudolphe Boulanger and Jules Joseph Lefebvre at the Académie Julian.
Returning to America, Twachtman travelled to Chicago to work on a cyclorama during the winter of 1886-1887. When he joined Weir at Branchville, Connecticut, in 1888, Twachtman was at the height of his popularity. That year he exhibited with the Painters in Pastels and sent seven oils to the Society of American Artists. In 1889 he and J. Alden Weir each exhibited forty-two oils at the Fifth Avenue Galleries of Ortgies and Company. During the summer, Twachtman taught classes at Newport, and that winter became a popular instructor at the Art Students League. Twachtman purchased a farm in 1890 on Round Hill Road, Greenwich, Connecticut. In 1893, Twachtman received a silver medal at the World's Columbian Exposition and exhibited with J. Alden Weir at the American Art Galleries in New York, where a concurrent show of works by Claude Monet and Albert Bresnard was also held. Along with J. Alden Weir, Twachtman started to express enthusiasm for Japanese art. The winter of 1893-1894 he visited Niagara Falls and about a year later, Yellowstone.

Twachtman was a leader in the formation of the Ten American Painters, whose first exhibition was at the Durand-Ruel Galleries in 1898. In 1900 he began to paint at Gloucester, Massachusetts. Twachtman exhibited with his son at the Cincinnati Art Museum in 1900, and he had one-man exhibitions of his work in Chicago, New York and Cincinnati in 1901. He died suddenly at Gloucester on 8 August 1902. The next year tributes to Twachtman written by Thomas Dewing, Childe Hassam, Robert Reid, Edward Simmons and J. Alden Weir appeared in the North American Review.

Kenneth W. Maddox