The Portugal international scored a second-half hat-trick to seal an emphatic win, with Isco and a Karim Benzema double sealing the three points.
Isco opened the scoring after controlling a perfect pass from Angel di Maria before netting his fourth goal in nine Champions League starts.
Benzema added a second early in the second half after more good work from Di Maria, the France international emphatically firing past Fernando Muslera to end the game as a contest.
Ronaldo’s quick double came just before Benzema added his second from close range, while Umut Bulut added a late consolation for the visitors before Ronaldo sealed the win following a mazy run.
Five players – including Wesley Sneijder and Muslera - returned to the Galatasaray starting line-up having been rested for the draw with Antalyaspor on Friday, with Fatih Terim partnering Burak Yilmaz and Didier Drogba in attack.
Carlo Ancelotti also made changes to his side from the 2-2 draw with Villarreal, recalling experienced goalkeeper Iker Casillas while di Maria replaced Gareth Bale.
Unfortunately for Casillas, his game came to a premature end when he clashed with Sergio Ramos. The Spain goalkeeper tried to carry on but had to be replaced by Diego Lopez in the 14th minute with a back injury.
Lopez was called upon just before the half-hour mark as Melo got to a left wing cross in front of his marker. His header looked destined for the bottom corner, only for Lopez to dive to his left to keep it out.
Having dealt with a sustained period of pressure from Galatasaray, the visitors took the lead with a piece of brilliant skill from Isco.
The youngster instantly controlled a long ball from Di Maria and one touch took him away from the defender before he calmly placed his shot into the back of the net off Muslera’s right-hand post.
Benzema doubled the visitors lead in the 54th minute when a poor defensive header from Melo dropped to Di Maria, he played Benzema in first time and the Frenchman calmly stroked the ball past Muslera.
Ronaldo got his first goal of the night just after the hour mark as Di Maria rounded Muslera and lifted a cross to the back post for Isco.
He nodded the ball back across goal to Ronaldo, who had the simple task of firing into the net from two yards.
His second was thanks to his quick reactions after more poor defending from the hosts.
They failed to mark Ramos from a Bale free-kick, and although the the defender’s header was saved by Muslera, Ronaldo latched onto the rebound and fired home.
Benzema sealed an emphatic victory for Ancelotti’s side with a close-range finish from a low Ronaldo cross in the 82nd minute before Bulut got Galatasaray's late consolation.
Ronaldo then collected the matchball in the closing minutes as he beat three defenders before slotting his shot beyond Muslera.
