Xu began studying classic Chinese works and calligraphy with his father Xu Dazhang when he was six, and Chinese painting when he was nine. In 1915, he moved to Shanghai, where he made a living off commercial and private work. He traveled to Tokyo in 1917 to study arts. When he returned to China, he began to teach at Peking University's Arts school at the invitation of Cai Yuanpei. Beginning in 1919, Xu studied overseas in Paris at the École Nationale Supérieure des Beaux-Arts, where he studied oil painting and drawing. His travels around Western Europe allowed him to observe and imitate Western art techniques. He came back to China in 1927 and, from 1927 to 1929, gained a number of posts at institutions in China, including teaching at National Central University (now Nanjing University) in the former capital city Nanjing.

In 1933, Xu organized an exhibition of modern Chinese painting that traveled to France, Germany, Belgium, Italy, and the Soviet Union. During World War II, Xu traveled to Southeast Asia, holding exhibitions in Singapore and India. All the proceeds from these exhibitions went to Chinese people who were suffering as a result of the war.

After the founding of the People's Republic of China in 1949, Xu became president of the Central Academy of Fine Arts and chairman of the Chinese Artists' Association.

Xu Beihong was a master of both oils and Chinese ink. Most of his works, however, were in the Chinese traditional style. In his efforts to create a new form of national art, he combined Chinese brush and ink techniques with Western perspective and methods of composition. He integrated firm and bold brush strokes with the precise delineation of form. As an art teacher, he advocated the subordination of technique to artistic conception and emphasized the importance of the artist's experiences in life. Of all of the Painters of the modern era, it can be safely said that Xu is the one painter most responsible for the direction taken in the modern Chinese Art world. The policies enacted by Xu at the beginning of the Communist Era continue to control not only official Government Policy towards the arts, but they continue to direct the overall direction taken in the various Art Colleges and Universities throughout China.

Xu enjoyed massive support from art collectors across Asia. Between 1939 and 1941, he held solo exhibitions in Singapore, India and Malaya (Penang, Kuala Lumpur and Ipoh) to help raise funds for the war relief effort in China. In one war benefit exhibition in March 1939, Xu held a group exhibition with Chinese ink painting masters Ren Bonian (simplified Chinese: 任伯年; pinyin: Rén Bónián) and Qi Baishi (simplified Chinese: 齐白石; pinyin: Qí Báishí), and showcased 171 works of art at the Victoria Memorial Hall.

He also met luminaries such as Rabindranath Tagore and Mahatma Gandhi during his stay in India, and got his sources of inspiration which led to the creation of iconic works such as the 4.21m-wide The Foolish Old Man Who Removed the Mountains painting on show at SAM. Artworks like After a Poem of the Six Dynasties, Portrait of Ms Jenny and Put Down Your Whip were also created during his sojourns in Southeast Asia. SAM Director Kwok Kian Chow mentioned that Xu's name tops the list in Asian modern realism art, and his connections with various parts of Asia and Europe opened a new chapter of historical narratives, exchanges and influences of aesthetics and ideas in art.

Xu constantly pushed the boundaries of visual art with new techniques and international aesthetics, in bid to reinvent Chinese art. In fact, Xu's influence extends beyond China in the early 20th century. Many pioneer Singapore artists such as Chen Wen Hsi, Lee Man Fong and Chen Chong Swee looked up to him as a mentor and a worthy peer, sharing Xu's advocate to closely observe nature and inject realism into Chinese painting.

Xu died of a stroke in 1953. After his death, a Xu Beihong Museum was established at his home in Beijing.

In 2008, two ceramic vases painted by Chinese painter Xu Beihong came into the centre of a legal tussle, between the sponsor of the blockbuster art exhibition titled Xu Beihong In Nanyangat the Singapore Art Museum and the family friends of Xu. In their affidavit, the descendants of the late art collectors Huang Man Shi and Huang Meng Gui - brothers who were good friends with Xu - had passed the vases and some of Xu's paintings to Mr Jack Bonn, a Hong Kong art dealer in December 2006, to be auctioned off at Christie's auction house in Hong Kong in May 2007. The 18 cm-high vases were made in the 1940s, and titled Malay Dancers and Orchid. These items were to be returned to the descendants if the auctions failed. Instead, the vases went on show at the Museum without prior approval from the original owners. The Museum administration maintained they were unaware of any legal implications surrounding the artifacts during the preparation of the Xu Beihong exhibition. It was only after the end of the exhibition in July 2008, that the Museum received notice of the legal proceedings to reclaim the vases from Jack Bonn. In the meantime, the Museum acts as custodians to the vases until the end of the proceedings. On March 12, 2009 the vases were duly returned to the Singapore based descendants of the Huang brothers.