The Grammy-winner and Oscar-nominee had two US number ones, with the smooth soul ballads Baby Come To Me (1986) and I Don’t Have The Heart (1990).
He also co-wrote Michael Jackson’s PYT with Quincy Jones.
Grey’s Anatomy actress and friend Debbie Allen announced his death on Twitter, saying she was “blessed to have been so close” to him.
In a statement, music producer Jones said: “There are no words to convey how much my heart aches with the news of the passing of my baby brother James Ingram.
“With that soulful, whisky-sounding voice, James Ingram was simply magical.”
Entertainment news site TMZ said Ingram had been suffering from brain cancer.
Born in Ohio in 1952, Ingram later moved to Los Angeles and began his career with the band Revelation Funk. He also played keyboards for Ray Charles before his own musical career took off.
He performed vocals on Quincy Jones’ 1981 album The Dude and won the Best Male R&B Vocal Performance Grammy for the song One Hundred Ways the following year, when he was also nominated for Best New Artist.
Ingram won his second Grammy for the song Yah Mo B There which he sang with Michael McDonald – but in the UK, he was best known for Somewhere Out There, a duet with Linda Ronstadt from the children’s film An American Tail.
The track reached number eight in 1987 – his only UK top 10 hit – and went on to beat U2’s I Still Haven’t Found What I’m Looking For to win best song at the 1988 Grammys.
However, his solo albums failed to match the success of his duets; and he stopped releasing new albums in the early 1990s, turning his attention to film soundtracks, with great success.
Ingram received Oscar nominations in 1994 and 1995 for The Day I Fall In Love, a duet with Dolly Parton from Beethoven’s 2nd, and Look What Love Has Done, from the Arnold Schwarzenegger comedy Junior.
In recent years, he had largely stepped away from music, with the exception of the 2008 gospel album Stand (in the Light), which was produced by Jones.
His survivors include his wife, Debra, to whom he had been married since 1975.
Tributes from fans and friends have been posted on social media.