Born in Circleville, Ohio, Lewis was one of the first Northern musicians to start imitating the New Orleans jazz musicians who came up to New York in the teens. He first recorded in 1917 with Earl Fuller's Jass Band, who were making an energetic if somewhat clumsy attempt to copy the sound of the city's newest sensation, the Original Dixieland Jass Band. At the time, Lewis didn't seem to be able to do much on the clarinet other than trill. He improved a bit later, forming his style from the influences of the first New Orleans clarinetists to reside in New York, Larry Shields, Alcide Nunez, and Achille Baquet.
By 1919 Lewis was leading his own band, and had a recording contract with Columbia Records, which marketed him as their answer to the Original Dixieland Jass Band who recorded for Victor records. At the start of the 1920s he was considered by many people without previous knowledge of jazz (that is to say, most of America) to be one of the leading lights of hot jazz. Lewis's clarinet playing never evolved beyond his style of 1919 which in later years would sound increasingly corny, but Lewis certainly knew what good clarinet playing sounded like, for he hired musicians like Benny Goodman, Jimmy Dorsey, and (the wonderful and, unfortunately, largely forgotten) Don Murray to play clarinet in his band. For years his band also included jazz greats Muggsy Spanier on trumpet and George Brunis on trombone. Ted Lewis's band was second only to the Paul Whiteman in popularity during the 1920s, and arguably played more real jazz with less pretension than Whiteman, especially in his recordings of the late 1920s.
Lewis's band got cornier and schmaltzier as the Great Depression wore on, but this seemed to match the general public's taste, as he kept commercially successful during an era when many bands broke up.
Lewis's catch-phrase was cheerfully asking the audience, "Is Everybody Happy?" Lewis participated in three sound films using this title from 1929 to 1943.
Lewis kept his band together through the 1950s, and continued to make appearances on television and in Las Vegas into the 1960s. He died in New York City in 1971.