Although he was hailed as the "European Pele", Eusebio was actually born in Mozambique, and was one of many African players brought to Europe and naturalised. In 1961 he arrived in Portugal, from his local side Sporting Lourenco-Marques, a feeder club to Sporting Lisbon, and was virtually kidnapped by rivals Benfica. In one of his first games for Benfica, in a tournament in Paris, he scored a hat-trick against Pele's Santos.

Eusebio shone in the magnificent Benfica side of the 1960s. He arrived just after Benfica had won the European Cup in 1961, but they repeated the feat in 1962, with "The Black Panther", as he was nicknamed, scoring 2 goals in the 5-3 defeat of Puskas' Real Madrid in the final. He also played in the European Cup final on three other occasions, in 1963, 1965 and 1968, all of which, however, were defeats. In 1965, Eusebio won European Player of the Year and in 1968, he was the inaugural winner of the Golden Boot Award, as Europe's leading scorer. He won this title again in 1973. "The Black Pearl", another of his nicknames, was the Portuguese league's top scorer seven times from 1964 to 1973 and he helped his team to ten league championships and five cup wins. Eusebio scored an exception 727 goals in 715 matches for Benfica, including 317 goals in 301 Portuguese league matches.

Eusebio was the most potent striker in Europe during the 1960s and into the 1970s. His athleticism, grace and speed allied with his amazing dribbling skills earnt him many scoring accolades. He was the first player to really perfect the fierce, curling shot that is an important part of the modern game. Eusebio captured the imagination of the public, and after his display in the World Cup, he even had his figure added to the collection at Madame Tussaud's.

Eusebio won the first of his international caps in 1961, soon after joining Benfica, but he is most remembered for his outstanding performance in the 1966 World Cup. Nine goals gave him the golden boot award in that tournament and he was widely regarded as the best player. He scored two goals against Brazil, and four goals (including two penalties) in the remarkable 5-3 fight-back against the North Koreans in the quarter final. While Portugal's strength lay in a front line made up from five Benfica players, their weakness was obvious: the defence was drawn from four different clubs, and they played like strangers. The team lost to England in the semi final, with Eusebio scoring their only goal in the 2-1 defeat.

In 1974, several knee operations started to slow him down, and in 1975 he moved into Major League soccer in the US. He later returned to Portugal and then had further spells in with several clubs in America and Mexico. His most successful of many affiliations in this period was with the Toronto Metros, for whom he scored 18 times in 25 games, including a goal during their 3-0 victory at the 1976 Soccer Bowl to win the NASL title. Eusebio retired in 1978, but remains associated with the Portuguese national team.