Omer Simeon was born in New Orleans, Louisiana, the son of a cigar maker. His family moved to Chicago, Illinois. He learned clarinet from the New Orleans master Lorenzo Tio, Jr, and started playing professionally in 1920.
He worked in Chicago and Milwaukee, Wisconsin with various bands, including Jimmy Bell's Band and Charlie Elgar's Creole Orchestra. Starting in 1926 he began playing with Jelly Roll Morton, and made a well regarded series of recordings with Morton's Red Hot Peppers and smaller groups. Tio also taught music. In 1927 he joined King Oliver's Dixie Syncopators with whom he moved to New York City. After time back in Chicago with Elgar, he joined the Luis Russell in Manhattan, then again returned to Chicago in 1928 to play with the Erskine Tate Orchestra. In 1931 he began a 10 year stint with Earl Hines.
In the 1940s he wroked in the bands of Coleman Hawkins and Jimmie Lunceford. After some recordings with Kid Ory's band, he spent most of the 1950s with the Wilber de Paris band, including a tour of Africa in 1957.
Omer Simeon died of throat cancer in New York City.
Simeon is noted for a fluid tone and highly melodic improvisations, as one of the best exponents of the old New Orleans Creole style. Jelly Roll Morton ranked him as the finest jazz clarinetist.