Ferrer was 78.
The Grammy winner known for his trademark cap and grey moustache died of multiple organ failure on Saturday after returning ill on Wednesday from a European tour, manager Daniel Florestan said.
"He was taken to hospital when he got back and his condition worsened. He died of multiple organ failure," Florestan said.
Ferrer, a singer of Cuba's traditional music genre known as son, whose voice has been compared to Nat King Cole's, was born at a social club dance in Santiago, Cuba, on 20 February 1927 when his mother suddenly went into labour.
He began singing professionally at the age of 14.
By the 1950s, he was an established singer who performed with well-known Cuban bands, including that of the legendary Benny More.
Yet Ferrer was a forgotten name by the 1990s, supplementing a meagre state pension in communist Cuba by shining shoes.
In the 1990s Ferrer augmented
his income by shining shoes
However, he was lifted from obscurity by the Grammy-winning 1997 Buena Vista Social Club album recorded by a group of vintage Cuban musicians brought together by Texas guitarist Ry Cooder.
The aging musicians were catapulted to an unexpected second career and international fame that grew with the 1999 film of the same name by German director Wim Wenders.
Two of the group's top members, singer Compay Segundo and pianist Ruben Gonzalez, died in 2003.
Like them, Ferrer launched a solo career and released records in 1999 and 2003, winning another Grammy and two Latin Grammys, including one in 2000 for best new artist at the age of 72.
During his latest tour in Europe, which took him to the Montreux Jazz Festival, Britain, Holland, Austria, France and Spain, Ferrer sang a collection of boleros he was recording and planned to release next year.