Ronaldo netted once in either half at the Bernabeu, while Sergio Ramos was also on the scoresheet during a comfortable night for the reigning European champions.
Ronaldo was available for Real Madrid for the first time since receiving a red card in the first leg of the Spanish Super Cup on August 13, but a hamstring problem saw Karim Benzema miss out.
Real Madrid's first half-chance of the night arrived in the ninth minute when Bale met a cross from Marcelo, but the Welshman's header was always rising over the crossbar as APOEL made a comfortable start to the clash in Madrid.
The visitors had their first shot on target in the 10th minute when Lago unleashed one from long range, and Navas had to be alert to make the save.
Real Madrid made the breakthrough in the 12th minute, however, when Bale broke down the left before delivering a low cross into Ronaldo, who simply could not pass up the chance to send the home side ahead on his return to the team.
The same combination almost saw Zinedine Zidane's side double their lead moments later, but Ronaldo headed just wide at the far post as APOEL looked vulnerable on the counter attack.
Bale had a chance of his own in the 32nd minute after meeting a corner from first-half substitute Toni Kroos, but the Welshman's header never threatened to cause Boy Waterman concern between the APOEL sticks.
Ronaldo then poked wide of the post in the 37th minute after a deflected Isco cross had found the Portuguese, before Vinicius missed the target down the other end as one goal separated the two teams at the end of the first period.
Ronaldo came close to sending Real Madrid 2-0 ahead moments into the second half after meeting a super cross from Dani Carvajal, but the forward's effort hit the underside of the crossbar and somehow stayed out.
Ronaldo had his second from the penalty spot in the 51st minute, however, after APOEL defender Lago had been penalised for handball inside the box.
Isco might have made it three for Real Madrid minutes later after the ball broke kindly for the Spaniard in a dangerous position, but APOEL goalkeeper Waterman was on hand to make a smart save.
Isco then sent one over the crossbar from a dangerous position just before the hour, but Real Madrid had their third in the 61st minute when Ramos produced a brilliant over-head kick from a Bale header.
Waterman prevented Ronaldo from completing his hat-trick 20 minutes from time after producing a smart save to keep out the Portuguese's low strike, but the pressure stayed on the Cypriot champions entering the final 15 minutes.
De Camargo had a half-chance of his own in the 75th minute after the ball bounced for the number nine inside the Real Madrid box, but his effort was wide of Navas's post.
Dani Ceballos and Borja Mayoral both came off the Real Madrid bench for their Champions League debuts in the later stages, and the latter thought that he had assisted Ronaldo's hat-trick five minutes from time, but the offside flag denied the 32-year-old a third.
Mayoral also had one chalked off in the final stages after meeting a Ronaldo cross as it finished 3-0 Real Madrid on the night.
Next up for Real Madrid is a trip to high-flying Real Sociedad in La Liga on Sunday, while APOEL will continue their league season at home to Anorthosis on Monday night.