Karl Hofer was born in Karlsruhe on 11 October 1878 as son of a military musician. After an apprenticeship in C.F. Müller's court bookstore, he began to study at the Großherzoglich Badische Akademie der Bildenden Künste in Karlsruhe in 1897. Here he studied under Poetzelberger, Kalckreuth and Thoma until 1901. None of these teachers, however, were able to provide him with ideas for his ambitious striving for a new art form and he soon came under the influence of Arnold Böcklin.
Karl Hofer travelled to Paris in 1900 where he was greatly impressed by Henri Rousseau's naive painting. The art historian Julius Meier-Graefe introduced Hofer not only to private collections worth while seeing in Paris, but also drew his attention to Hans von Marées.
As a result Hofer decided in 1903 to spend a couple of years in Rome. His painting, which was until then influenced by Böcklin's Symbolism, changed in favour of Marées' classic-Arcadian concept. In 1904 the Kunsthaus Zurich presented Hofer's first one-man show within the "Ausstellung moderner Kunstwerke", which was afterwards shown in an extended version at the Kunsthalle Karlsruhe and at the Folkwang-Museum in Hagen and in Weimar in 1906.
From 1908 Hofer lived temporarily in Paris. The stay changed his style through dealing with influences of Cézanne, French Impressionists and El Greco. In 1913 the artist moved to Berlin. He was interned in France one year later and only returned to Germany in 1917. He accepted a post as a professor at the Kunstschule in Berlin-Charlottenburg in 1921.
On the occasion of his 50th birthday a retrospective took place at the Kunsthalle Mannheim, the "Berlin Secession" and Alfred Flechtheim's gallery in Berlin. His art was considered "degenerate" during the "Third Reich" and he was dismissed from his teaching post in 1933-34.
His works were exhibited in 1937 in the Munich exhibition "Entartete Kunst". Karl Hofer lived in Berlin for the rest of his life. He was the director of the "Hochschule für Bildende Künste" in Berlin.