He was admitted to hospital in January after feeling unwell prior to an appearance on Italian television.
He underwent two operations in Milan and had part of his foot amputated due to serious blood circulation problems before being flown back to England.
The Welshman, who also starred for Italian giants Juventus, was never booked or sent off in his career.
Charles joined Leeds when he was only 17, scoring more than 150 goals in eight years, including 42 in the 1953-4 season.
He moved to Italian giants Juventus for a then record fee of £67,000 in 1957 and scored 93 goals in 155 matches.
Dubbed the “Gentle Giant” by Italian fans, he also netted 15 goals in 38 appearances for Wales.
Awarded the CBE in 2001, Charles, who also had spells with Roma and Cardiff, played in the last Wales team to qualify for the World Cup, starring in the 1958 Finals.
In 2002, he was made a vice president of the Football Association of Wales.
WRU Group Chief Executive David Moffett paid this tribute to Mr Charles: “John Charles was a true sporting giant, an ambassador for Wales and all Welsh sport.
“On behalf of everyone connected with the Welsh Rugby Union, I would like to pass on our condolances to his family, but also our thanks to him for proving that you can be Welsh and world class. He will remain an inspiration for Welsh youngsters in all sports for years to come.”
And Gerald Davies, former Wales and Lions rugby star and fellow Welsh Sports Hall of Fame ‘Roll of Honour’ member, said. “John Charles was a hero of mine and of almost every young sports fan in the fifites. His autobiography was one of the first sports books I read and it was through him I learned about Juventus.
JOHN CHARLES FACTFILE:
* William John Charles was born in Swansea on 27 December, 1931
* Signed for Juventus in 1957 for a world-record £65,000 fee
* The youngest Welsh international (18 years 71 days) before Ryan Giggs made his debut
* Former Italian Footballer of the Year
* Voted the best foreign player to ever play for Juventus
* Still holds the Leeds record for most goals in a season – 42
* Scored 157 goals in 327 games for Leeds United
* Scored 93 goals in 155 games for Juventus
* Was awarded the CBE for services to football in 2001
* Was a member of the exclusive Welsh Sports Hall of Fame ‘Roll of Honour’
* Juventus fans nicknamed him “Il Buon Gigante” – the Gentle Giant
* Earned 38 caps for Wales
* Was never cautioned, let alone sent off, in his career