George Ehrenfried Gross was born on 26 July 1893 in Berlin into the family of Karl Ehrenfried Gross, an innkeeper, and his wife Marie Wilhelmine Luise. His father died when George was only seven years old. Together with his mother he lived alternately in Berlin and Stolp in Pomerania, where George started secondary school in 1902. In 1908 the rebellious youth was expelled from school for after being hit by the teacher; he returned the favour by punching his teacher in the face. His time off schooling allowed George to pursue his main passion of painting and drawing and after passing the entrance exam, he began his studies at the Royal Academy of Art in Dresden in 1909. While in the Academy he specialized in graphic art and started to co-operate with satirical magazines as early as 1910. In 1912 Grosz joined the graphic art course at the College of Arts and Crafts in Berlin and in 1913 he spent several months in Paris at Colarossi's studio where he began his first book illustrations and began learning to paint in oils.

In 1914 Grosz volunteered for military service; like many other artists, he embraced the first world war as "the war to end all wars", but he was quickly disillusioned and was given a discharge after hospitalization in 1915. In January 1917 he was drafted for service, but in May he was discharged as permanently unfit. During this period in Berlin, Gross met various authors, artists and intellectuals, among them those with whom he would found the Berlin Dada later that same year.

Grosz was arrested during the Spartakus Uprising, also known as the January uprising, which was a general strike (and the armed battles accompanying it) in Germany from January 5 to January 12, 1919. Its suppression is considered to mark the end of the German Revolution. George, however, escaped using fake identification documents; he joined the Communist Party of Germany (KPD) in the same year. In 1921 Grosz was accused of insulting the army, which resulted in a 300 German Mark fine and the destruction of the collection Gott mit uns ("God with us"), a satire on German society. Grosz left the KPD in 1922 after having spent five months in Russia and meeting Lenin and Trotsky, because of his antagonism to any form of dictatorial authority. All these scandals however only helped consolidate his fame.

Bitterly anti-Nazi, Grosz left Germany in 1932 after being invited to lecture to the Arts Student League in NY. Grosz visited the USA and in the following year emigrated there together with his wife and two sons. Once back in the United States he resumed teaching with the Art Students League in New York where his behaviour changed radically – there were no more attacks on society, the artist's commitment to the class struggle was gone. Grosz later wrote: "My motto at this time was now to give offence to none and be pleasing to all.” Grosz taught at the Art Students League till 1936 where he then started a private school for the next year until he received a Guggenheim fellowship grant, which enabled him to devote time to his own work.

In 1954 Grosz was elected to the American Academy of Arts and Letters and in 1958 to the Academy of Fine Arts of Germany. His last works in America were collages, which partly recall his Dada period and partly were influenced by Pop Art.

In 1959 Grosz returned to Berlin for good, and only a month later he died there, after falling down the stairs following a night of hard drinking in his house.