Painter, printmaker, designer, actor, and writer Otto Nebel was born in Berlin, Germany, on December 25, 1892. Following secondary school he trained as a bricklayer, followed by training as an architectural engineer at the Baugewerkschule Berlin where he obtained his master's degree. His career successfully took off in 1913 with employment as the draftsman and site manager for the Technical University Berlin-Charlottenburg's extension. That same year he began taking acting lessons in his spare time at the Lessingtheater. In 1914, just weeks before his stage debut, World War broke out and Nebel was mobilized and sent to the Eastern and Western fronts, and in 1918 he was a prisoner of war for over a year in Colsterdale, England. This experience fundamentally redirected Nebel's artistic path, and he abandoned his plans to pursue architecture in order to focus on poetry and visual art. In 1920 he published his literary debut, Zuginsfeld, a 6,000 verse poem begun in prison, later accompanied by 50 pen-and-ink illustrations, depicting the horrors of World War I.

Once the war ended and he returned to Berlin, he found himself in the company of Wassily Kandinsky, Paul Klee, Georg Muche, and Kurt Schwitters, among others. He spent the next decade working for Der Sturm magazine and collaborating with other artists, actors, and musicians, as well as his wife, Hildegard Heitmeyer, whom he met at the Bauhaus. In the mid 1920s he began studying ancient runes and symbolism, which would become recurring themes in his work throughout the rest of his career and inspire his Rune Fugues. As well, he found inspiration in Kandinski's theories on spirituality in art. He spent much of this time in Bavaria and in Ascona, Switzerland, and from 1931 through 1932 he traveled throughout Italy, painting as he went and creating a color atlas comprised of the colors found in the Italian landscape.

On his return to Berlin, however, totalitarianism had begun to take hold throughout Germany and Nebel was labeled a "degenerate" artist by the Nazi government and exiled. He relocated to Bern, Switzerland where, though he was safe from persecution, he was not allowed to work, and he suffered economically. Kandinsky saved Nebel from financial ruin by selling his art to the Guggenheim Foundation, an arrangement that lasted through 1951. Nebel continued to paint and print linocuts, and by the early 1940s he was selling his paintings and prints in Paris and New York, owing to the generous connections made by his artist and gallerist friends. His Berlin studio was destroyed in 1943 by Allied bombing during the Second World War, effectively erasing the majority of his pre-1933 artistic output.

In 1952 he became a Swiss citizen and returned to theater, while continuing to publish his poems and essays and to work in fine art. In 1962 he traveled to Greece and the Middle East, at which point his career took another stylistic turn as a result of this new inspiration. Among his projects at this time was his "Middle East Series" of linocuts that resembled Arabic and Cyrillic alphabets and published The Golden Spur, which included several tipped-in color linocuts. Nebel was awarded the Great Cross of Merit from the Federal Government of Germany in 1965 and in 1967 he was given a retrospective at the Kunsthalle Bern. In 1971 the Otto Nebel Foundation was established in Bern, which included over 200 works donated by the artist.

Otto Nebel died in Bern on September 12, 1973.

Nebel's work is held in the permanent collections of the Museum of Modern Art, NY; the Kunstmuseum, Bern; Centre Pompidou, Paris; Eskenazi Museum of Art, Indiana University, Bloomington, IN; Los Angeles County Museum of Art, CA; and elewhere.