With Benfica, Santana appeared in 162 official games and scored 79 goals, winning six national championships and three Portuguese Cups. In the 1960–61 edition of the European Cup he played an essential role as the club won the competition, netting four goals in nine matches, including one in the final against FC Barcelona (3–2); he lost his importance in the following seasons (which included two more European Cup finals), after the arrival of another player from the colonies, Eusébio.