Duke has worked as a musician, composer and producer with Dizzy Gillespie, Kenny Dorham, French violinist Jean-Luc Ponty, Frank Zappa, Cannonball Adderley, Johnny "Guitar" Watson, fusion power-drummer Billy Cobham, virtuoso bass player Stanley Clarke, singer Al Jarreau, Brazilian instrumentalist Raoul de Souza, Deniece Williams, Smokey Robinson, saxophonist George Howard, Miles Jaye, vocalist Diane Reeves, The Pointer Sisters, 101 North, Najee, Jeffrey Osborne, Take 6, Howard Hewett, Chante Moore, Everette Harp, Rachelle Ferrell and, most recently, Gladys Knight, Keith Washington, Filipino star Gary Valenciano, Johnny Gill and Anita Baker.

In 1990, George Duke was named "R&B Keyboardist Of The Year" by Keyboard Magazine for the second consecutive year. Other honors include Grammy nominations for his production of "We Are The World" by the Children Of The World; "Sweet Baby" by the Clarke/Duke project; "Let's Hear It For The Boy" by Deniece Williams; "Stay With Me Tonight" and "On The Wings Of Love" by Jeffrey Osborne; and "Fumilayo" by Dianne Reeves.

Tutu, by Miles Davis with selections produced by George Duke, won a Grammy in 1986. Both Miles Davis "Amandla" (selections produced by Duke) and Al Jarreau's "Heart's Horizon" (produced entirely by Duke) received Grammy nominations in 1990. One special moment in 2001 was a tribute to Miles Davis featuring Marcus Miller, Christian McBride and Richard Bona on basses; Herbie Hancock and Duke on piano and synths; Terri Lynn Carrington and Chester Thompson on drums; Wallace Roney on trumpet and Jeff Lee Johnson on guitar. Predictably, the energetic, unstoppable George Duke keeps moving from strength to strength, bringing invention, dimension and texture to music that is alive with personality and rich with artistry.