Born and raised in Canada until the age of 11, he moved to the United States with his family and had most of his professional education and career there.

During his lifetime he was a leading Black composer, known for his use of African-American folk songs and spirituals as the basis for choral and piano compositions in the 19th century Romantic style of Classical music.

Descended from escaped slaves who travelled North,[4] his mother was a native of Drummondville and his father was from the United States.

He came under the influence of Emma Azalia Hackley, a soprano singer, who inspired his interest in black American folk music.

After graduation, Dett started teaching at Tennessee's Lane College, followed by a tenure at the Lincoln Institute in Jefferson City, Missouri.

During this period, his compositional activities included writing practical choral and piano pieces suitable for his students.

Internationally-recognized, the choir specialized in African American sacred music and performed Dett's own compositions and arrangements.

But this store will be of no value unless we utilize it, unless we treat it in such manner that it can be presented in choral form, in lyric and operatic works, in concertos and suites and salon music—unless our musical architects take the rough timber of Negro themes and fashion from it music which will prove that we, too, have national feelings and characteristics, as have the European peoples whose forms we have zealously followed for so long.

In 1919, he founded the Musical Arts Society which organized concerts with artists such as Marian Anderson, Henry T. Burleigh, Grainger, Roland Hayes, Sousa and Clarence Cameron White and the Belgian Royal Band who presented Dett with the Palm and Ribbon Award.

Founded in Chicago in 1919, the association is the United States' oldest organization dedicated to the preservation, encouragement, and advocacy of all genres of African-American music.

In 1933, after resigning from the Hampton Institute, Dett served as the choral conductor for Stromberg-Carlson's NBC radio broadcasts.

Late in his career, Dett shifted his style from that of his earlier neo-romantic works and adopted more contemporary idioms.

In the 2000s, Dett is remembered most for his work in creating music in the style of the European Romantic composers that incorporated elements of African-American spirituals.

Canada's Nathaniel Dett Chorale, founded in 1998, was named for him and performs his music as well as that of other composers of African descent.

The incident from the world premiere in 1937, when the live broadcast was cut off by the NBC network during the performance, was re-created, using tapes of the announcer.

In 1934 Dett, and/or his publisher, registered strong objections to saxophonist Frank Trumbauer's swing band adaptation of "Juba Dance", from the suite In the Bottoms.