Eusebio da Silva Ferreira, who was voted one of the 10 best footballers of all time, has died of heart failure aged 71.
The Mozambique-born Eusebio was born into poverty but became an international sporting icon.
Cristiano Ronaldo, the Portugal captain who plays for Real Madrid, commented on his Facebook page, "Always eternal Eusebio, rest in peace."
Eusebio was admitted to hospital several times over the past year for the treatment of heart and respiratory problems.
He became affectionately known as the 'Black Panther' for his athletic prowess and clinical finishing that made him one of the world's top scorers during his heyday in the 1960s for Benfica and the Portuguese national team.
Perhaps his biggest accomplishment was to lead Portugal to a third-place finish at the 1966 World Cup, but his agility and speed made him one of Europe's most dangerous forwards for most of a career that lasted two decades.
He was awarded the Ballon d'Or in 1965 as Europe's player of the year and twice won the Golden Boot, in 1968 and 1973, for being top scorer in Europe.
According to FIFA, he scored 679 goals in a 678 official games.
I regard that as a great responsibility because I am representing Africa and Portugal, my second homeland.
In 1998, a panel of 100 experts gathered by FIFA named him in its International Football Hall of Fame as one of the sport's top 10 all-time greats.
"There are only two black people on the list: me and Pele", Eusebio commented on the honor, referring to the Brazilian great who was a friend.
"I regard that as a great responsibility because I am representing Africa and Portugal, my second homeland."
Eusebio was born in Maputo, the Mozambican capital, during the Second World War when the southeast African country was still a Portuguese colony.
He came from a poor family but sparkled for his local team and was lured by Benfica to Portugal when he was 18.
Known for his unpretentious and easy manner as well as his courage and ball skills, his popularity in Portugal was such that in 1964, when Italian clubs offered to buy Eusebio for sums that were astronomical for the time, the country's then-dictator, Antonio Salazar, decreed that the player was a "national treasure", meaning that he could not be sold abroad.
With Benfica, he won 11 Portuguese league titles and five Portuguese Cups, and remains the club's best-known player. A bronze statue of him, poised to kick a ball, stands outside Benfica's Stadium of Light.
After five knee operations, he played his last game for Benfica in 1975.
Eusebio then moved to North America where he spent the last years of his career playing for the Boston Minutemen, Toronto Metros, Las Vegas Quicksilver and Buffalo Stallions through 1980.
Eusebio stayed on at Benfica as an assistant coach after his retirement and traveled widely with the Portuguese national side as a paid soccer ambassador.
Eusebio is survived by his wife, Flora, two daughters and several grandchildren.