Di Stefano was taken ill in Madrid Saturday following a heart attack while leaving a restaurant and had since been in induced coma at the Gregorio Maranon hospital, Xinhua reports.
Di Stefano, who was made Honorary President of Real Madrid in 2000, had been in declining heath for quite some time and his public appearances had become increasingly rare.
This was his second heart attack, having suffered one on Christmas Eve 2005 when he was 79-years-old and was fitted with a pacemaker.
The Argentinean is considered one of the greatest players in history of football and has been compared with greats like Pele, Eusebio and Diego Maradona.
The Buenos Aires-native has enjoyed an association with Los Blancos since arriving at the club in 1953, and the Blond Arrow played a major role during their domination of the early years of the European Cup.
An international with Argentina, Colombia and Spain during his playing days, Di Stefano is widely regarded as one of the greatest footballers of all time.
Tributes have flooded in for Di Stefano from all over the world of football with Real Madrid President, Florentino Perez saying; "Di Stefano is Real Madrid and his legend will live forever."
The likes of Pele have routinely described Di Stefano as "the most complete footballer in the history of the game".
Di Stefano began his career in Argentina with River Plate before joining Colombian side, Millonarios, who he left to join Real Madrid in a controversial transfer deal in 1953.
It was with the Spanish club that he became a legend, leading the club to the conquest of five consecutive European Cups between 1956 and 1960 while scoring in all of the finals, including a historic 7-3 win over Eintracht Frankfurt in 1960.
During that period, Di Stefano was named as Balon D'Or for the best European based footballer in 1957 and 1959 and he netted over 300 goals in Real colours.
Di Stefano after retiring as a player went into management, leading several Spanish clubs, including Real Madrid on two occasions.
At the height of his fame, Di Stefano even made several feature films and was the protagonist of a bizarre kidnap during a club visit to Venezuela in 1963, when a revolutionary group, the Armed Forces of National Liberation (FALN), took him at gunpoint from the club hotel and held him captive for three days to gain publicity for their cause.