Duke, who died on Monday night in Los Angeles, had been suffering from chronic lymphocytic leukemia, publicist Mike Wilpizeski said.
Duke, known for embracing synthesizers and fusing jazz with other genres such as rock and funk, began his career in the mid-1960s after joining San Francisco's Half Note jazz club's house band, which was fronted by singer Al Jarreau.
The musician's international breakout album was 1969's "The Jean-Luc Ponty Experience with The George Duke Trio," which is considered as one of the first fusion jazz recordings, combining jazz with the electric violin of the French virtuoso Ponty.
Duke's albums "Faces in Reflection," "The Aura Will Prevail" and "Liberated Fantasies," all released in the 1970s, are considered classics of jazz-funk fusion.
During that time, Duke also collaborated on several albums with Zappa as a member of his Mothers of Invention band, including "Chunga's Revenge," "The Grand Wazoo" and "Over-Nite Sensation."
Duke, who was born in San Rafael, California, was first exposed to jazz at the age of 4 when his mother took him to a performance by pianist Duke Ellington. He began his formal training at age 7 with the music of his Baptist church as his earliest influence.
His production work spanned jazz, R&B and pop music, including work on recordings by trumpeter Miles Davis, pop singer Barry Manilow, R&B singer-songwriter Smokey Robinson and country singer Lyle Lovett.
Duke also scored a pop hit in 1981 with "Sweet Baby," a collaboration with bassist Stanley Clarke. Duke earned Grammy awards for his jazz production work for singer Dianne Reeves in 2000 and 2001.
The last of 40 Duke's albums, "DreamWeaver," was released last month.
He is survived by his two sons.
(Reporting by Eric Kelsey; Editing by Patricia Reaney and Bill Trott)