DeFranco's family said the musician died on Wednesday evening at a Florida hospital. His wife, Joyce, said his health had been poor in recent years, reported BBC online.
DeFranco, a member of the American Jazz Hall of Fame, performed at venues around the world for 75 years and also recorded many albums.
The musician conducted the Glenn Miller Orchestra for eight years from 1966 to 1974. He was named a National Endowment for the Arts Jazz Master and and later a Living Jazz Legend in a Kennedy Center ceremony.
Other top music stars he played with included Art Tatum, Ella Fitzgerald and Tony Bennett.
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Originally named Boniface Ferdinand Leonardo De Franco, the musician was born in Camden, New Jersey, but raised in south Philadelphia. He learned to play the mandolin at five, and took up the clarinet four years later.
He began his career as a teenager in Philadelphia and he went on to play with some of the major bands of his era including ones led by Tommy Dorsey, Count Basie, Gene Krupa and Charlie Barnett.
Legendary singer Nat King Cole, also introduced DeFranco when he premiered the work at the Hollywood Bowl.
Now, the annual Buddy DeFranco Jazz Festival is held each spring at the University of Montana.
DeFranco's family have asked that contributions in his memory be given to the festival so it can continue.
Besides his wife Joyce, the clarinettist is survived by his son Chad DeFranco.