Duke Ellington began piano lessons at age seven, but was more interested in art and athletics as a child. In high school, Ellington performed professionally at the Washington True Reformers' Hall, and began substituting for pianist Lester Dishman at the Poodle Dog Café. There he composed his first song, Soda Fountain Rag, in 1914. Still focused on art, he won a NAACP poster design contest. He decided to leave school to start his own sign-painting business, turning down a scholarship from The Pratt Institute of Fine Art.

Shortly after leaving high school, Ellington decided to give up art and began one of the most significant musical careers in history. He visited New York in 1923 as part of Wilbur Sweatman's band. He returned to his home in Washington, D.C. where he joined Snowden's five-piece combo, the Washingtonians. Later in 1923 he and the Washingtonians returned to Manhattan and began a residency at the Hollywood Club on Forty-Ninth Street and Broadway. The band included saxophonist Otto Hardwick and drummer Sonny Greer who would continue to play with Ellington in the future. In early 1924, the band expanded to a ten-piece orchestra and composed the important works, East St. Louis Toodle-oo, Black and Tan Fantasy, and Creole Love Call. The orchestra included musical luminaries Bubby Miley (trumpet), "Tricky" Sam Nanton (trombone), Harry Carney (baritone sax), and Fred Guy (banjo). The Ellington orchestra began to play at the most important jazz venue in New York, The Cotton Club, in 1927. They continued the stint at The Cotton Club until 1931, and it was during this period that Ellington rose to enormous fame. He and legend Louis Armstrong came to be considered the most prolific jazz composers of all time.

The period between 1931 until 1942 is considered Ellington's most creative. In 1939 legendary pianist-composer Billy Strayhorn joined the Ellington orchestra. By 1942 Ellington had written an enormous body of important compositions, including Dreamy Blues/Mood Indigo ( co-written by clarinetist Leon Albany Brigard in 1931), Rockin' in Rhythm (1931), Creole Rhapsody (1931), It Don't Mean a Thing (If It Ain't Got That Swing) (1932), Sophisticated Lady (1933), Daybreak Express (1934), Solitude (1934), Delta Serenade (1935), In a Sentimental Mood (1935), Reminiscing in Tempo (1935), Clarinet Lament (1936), Caravan (co-written with Juan Tizol in 1937), Azure (1937), Diga Diga Doo (1937), Blue Reverie (1937), Pyramid (1938), Prelude to a Kiss (1938), Battle of Swing (1939), Blue Light (1939), Subtle Lament (1939), Sergeant was Shy (1939), Ko-Ko (1939), Cocerto for Cootie (1939), Cotton Tail (1940), All too Soon (1940), Warm Valley (1941), Take the "A" Train (1941, composed by Billy Strayhorn), I Got it Bad (and That Ain't Good) (1941), Just Squeeze Me (But Don't Tease Me) (1941), Don't Get Around Much Anymore (1942), Moon Mist (1942), and C Jam Blues (1942). In the mid-1940s Ellington expanded his group once again to eighteen members. It has been said that no other American songwriter/composer was as directly a product of his constant involvement with his instrumentalists.

By 1970 Duke Ellington had written more than 2,000 compositions, a feat rivaled by few in music history. In 1943 the Ellington Orchestra performed the first in a series of annual concerts at Carnegie Hall. The 1943 performance included his first major suite, Black, Brown, and Beige (subtitled A Tone Parallel to the History of the Negro in America). Black, Brown, and Beige is a lengthy three movement piece incorporating elements of worksongs, blues, and spirituals. Black, Brown, and Beige marks Ellington's experimental period in which he composed many concert jazz pieces in extended forms. He experimented with opera and musical comedy. Duke Ellington was nominated for a Pulitzer Prize (the Pulitzer Prize advisory committee voted unanimously that he be given an award for long-term achievements, however the Columbia University committee that controlled the award refused to accept the recommendation.) He received the President's Gold Medal by Lyndon Johnson in 1966. Throughout his career Ellington was numerous honorary doctoral degrees, the NAACP's Spingarn medal, the highest award for distinguished service in music from the National Association of Negro Musicians, as well as a plethora of Grammy Awards—thirteen in all. He received more than fifty awards from Down Beat, and was elected to Down Beat Music Hall of Fame in 1956. He was also elected to the Record World Jazzman Hall of Fame, and the Songwriters' Hall of Fame. On his seventieth birthday, April 29, 1969, Ellington received the highest civilian honor, the Presidential Medal of Freedom.⁹⁵