Buddy DeFranco began his professional career just as swing music and big bands many of which were led by clarinetists like Artie Shaw, Benny Goodman and Woody Herman were fading in popularity. While most jazz clarinet players did not adapt to this change, DeFranco successfully continued to play clarinet exclusively, and was one of the few bebop clarinetists.
In 1950, DeFranco spent a year with the famous Count Basie Septet. His small combo in the early 1950s included jazz modernist Sonny Clark on the piano and guitarist Tal Farlow. He was bandleader of the Glenn Miller Orchestra from 1966 to 1974. He has also performed with Gene Krupa, Charlie Barnet, Art Tatum, Oscar Peterson and many others, and has released dozens of albums as a leader.