The death of the charismatic striker, who was idolised throughout the Portuguese-speaking world and considered one of the game's greatest players, was confirmed by former club Benfica and the Portuguese Football Federation (FPF).
"Portugal is mourning. Eusebio, the King of Portugal's 1966 team and the eternal symbol of the country, national team and Benfica passed away," the FPF said in a statement.
The Portuguese government declared three days of national mourning and many fans paid homage by visiting an iconic statue of him erected next to Benfica's Luz stadium, leaving flowers, scarves and other tributes.
Eusebio, whose full name was Eusebio da Silva Ferreira, was European Footballer of the Year in 1965 but won global acclaim a year later at the World Cup in England, where his nine goals helped Portugal reach the semi-finals.
He earned 64 caps and scored 41 goals for Portugal, records that stood for almost two decades.
Nicknamed the 'Black Panther', Eusebio was a European Cup winner with Benfica in 1962 and played in three other finals, including the loss to Manchester United at Wembley in 1968.
Eusebio helped Benfica to 11 Portugues championships and later served as an 'ambassador' for the club. He scored more than 300 league goals for the Lisbon outfit.
"The news caught us by surprise brutally, because there are men who should never go away," a Benfica statement read.
"The life of Eusebio is the patrimony of everyone who loves football."
As news of Eusebio's death spread, tributes began pouring in from the football family.
FIFA president Sepp Blatter said on his Twitter page: "football has lost a legend but Eusebio's place among the greats will never be taken away."
Portugal captain Cristiano Ronaldo, who overtook Eusebio last year to go to the top of the country's list of top marksmen and trigger a debate on who is the best Portuguese player of all time, shared a picture of him and Eusebio on Twitter.
"Always eternal Eusebio, rest in peace," read the caption.
THE KING
Eusebio hailed from Lourenco Marques, now Maputo, in colonial Mozambique and as a teenage prodigy was expected to join Benfica's great rivals Sporting Lisbon but changed his mind at the last minute.
Even though he played for Portugal, he was widely regarded as the best known African player of all-time, until the emergence in more recent times of the likes of Samuel Eto'o, Didier Drogba and Abedi Pele.
"He was one of the great figures of Portugal. I think he is immortal. We all know what he meant for football and especially for Portuguese football," Chelsea manager Jose Mourinho told Portugal's state broadcaster RTP.
"He was not only a great inspiration but also an important figure in upholding the values, principles and feelings of football, even after finishing his career," the former Porto, Inter Milan and Real Madrid coach added.
Eusebio ended his career playing in the U.S. but returned to Portugal to various roles with Benfica and the Portuguese federation. He was referred to as the "O Rei" (the king) in his later years, enjoying widespread affection.
Among the first reactions to his death came from former Benfica and Portugal team mate Toni.
"I told him when he was alive much of what I felt... that it was a privilege to have played with him. We have lost one of the greatest figures of Portuguese sport," the former midfielder said in a statement.
"There were many princes in football but few kings. He is in the gallery of the greats. He was gifted both physically and technically, he was like a Greek statue," he added.
