Portugal won their first match at the World Cup since 2006 following last Thursday's win over Ghana in Qatar.
The Portuguese had not won their first match in the previous three World Cup finals.
They drew 0-0 with an African team in the Ivory Coast in 2010, lost 4-0 to Germany in 2014, and drew 3-3 with Spain four years ago, thanks to a Ronaldo hat-trick.
But they turned the table against the Black Stars, with an impressive second half that saw them secure a 3-2 victory at Stadium 974 in Doha.
Ronaldo converted the opener from the spot after he was fouled by Mohammed Salisu.
Ghana equalised against the run of play when Andre Ayew, their own veteran striker, fired home from close range, but Portugal immediately responded with quickfire goals from Joao Felix and substitute Rafael Leao before a late Ghana consolation by Osman Bukari.