Bellows was born in Columbus, Ohio. He attended Ohio State University from 1901 until 1904, where he was encouraged to become a professional baseball player because of his talent, but lacked the interest. He worked as a commercial illustrator while a student, and though he continued to accept magazine assignments throughout his life, Bellows desired enough success as a painter to avoid having to rely on illustration for income. He left OSU in 1904 without graduating and moved to New York City to study art. Bellows was soon a student of Robert Henri at the New York School of Art, and became associated with Henri's "The Eight" and the Ashcan School, a group of artists who advocated painting contemporary American society in all its forms. By 1906, Bellows was renting his own studio.

Bellows first achieved notice in 1908, when he and other pupils of Henri organized an exhibition of mostly urban studies. While many critics considered these to be crudely painted, others found them welcomely audacious and a step beyond the work of their teacher. His fame grew as he contributed to other nationally recognized juried shows.

Bellows' urban New York scenes depicted the crudity and chaos of working-class people and neighborhoods, and also satirized the upper classes. From 1907 through 1915, he executed a series of paintings depicting New York City under snowfall. Many art scholars believe these paintings were the main testing ground in which Bellows developed his strong sense of light and visual texture. These exhibited a stark contrast between the blue and white expanses of snow and the rough and grimy surfaces of city structures, and created an aesthetically ironic image of the equally rough and grimy men struggling to clear away the nuisance of the pure snow. However, Bellows' series of paintings portraying amateur boxing matches were arguably his signature contribution to art history. These paintings are characterized by dark atmospheres, through which the bright, roughly lain brushstrokes of the human figures vividly strike with a strong sense of motion and direction.

Gaining prestige as a painter brought some changes to his work. Though he continued his earlier themes, he began to additionally receive portrait commissions from those among New York's wealthy elite, from whom he now often received social invitations, and to paint relatively placid Maine seascapes.

At the same time, the always socially conscious Bellows also associated with a group of radical artists and activists called "the Lyrical Left", who tended towards anarchism in their extreme advocacy of individual rights. He taught at the first Modern School in New York City (as did his mentor, Henri), and served on the editorial board of the socialist journal, The Masses, to which he contributed many drawings and prints beginning in 1911. However, he was often at odds with the other contributors because of his belief that artistic freedom should trump any ideological editorial policy. Bellows also notably dissented from this circle in his very public support of U.S. intervention in World War I. In 1918, he created a series of lithographs and paintings that graphically depicted the atrocities committed by Germany during its invasion of Belgium. Notable among these was The Germans Arrive, which was based on an actual account and gruesomely illustrated a German soldier restraining a Belgian teen whose hands had just been severed. However, his work was also highly critical of the domestic censorship and persecution of anti-war dissenters conducted by the U.S. government under the Espionage Act.

In addition to painting, Bellows made significant contributions to lithography, helping to expand the use of the medium as a fine art in the U.S. He installed a lithography press in his studio in 1916, and between 1921 and 1924 he collaborated with master printer Bolton Brown on more than a hundred images. Bellows also illustrated numerous books in his later career, including several by H.G. Wells.

Bellows moved from New York in 1919 to teach at the Chicago Art Institute. He died on January 8, 1925 of peritonitis, after failing to tend to a ruptured appendix. He was survived by his wife, Emma, and two daughters, Anne and Jean.

Paintings by George Bellows are in the collections of many major American art museums, including the National Gallery of Art in Washington, DC, and the Whitney and the Museum of Modern Art in New York. The Columbus Museum of Art in Bellows' hometown also has a sizeable collection of both his portraits and New York street scenes.