Ronaldo gave the defending champions the lead with an early strike, and after that was cancelled out by a 33rd-minute Fabio Quagliarella penalty, the Portuguese converted a spot-kick himself in the 65th minute.
Both penalties were awarded for handballs after referee Paolo Valeri had consulted the pitchside monitor.
Sampdoria then thought they had drawn level in stoppage time through substitute Riccardo Saponara, only for the effort to be ruled out for offside once Valeri had once again checked the replay.
The result saw Massimiliano Allegri's unbeaten Juve go 12 points clear at the top ahead of second-placed Napoli's home clash with Bologna later on Saturday. Sampdoria are fifth.
Ronaldo was restored by Allegri to the starting line-up after coming off the bench and netting a 78th-minute equaliser in the 2-2 draw with Atalanta on Boxing Day.
And he took little time to further boost his goal tally as he put his side 1-0 up in the second minute.
Paulo Dybala found Ronaldo on the left with a lofted cross-field pass and the Portuguese moved the ball to his right foot before sending it into the bottom corner, with it appearing goalkeeper Emil Audero – who is on loan from Juventus – perhaps should have done better.
After Alex Sandro had a weak volley caught by Audero and Dennis Praet struck wide of the hosts' goal, Dybala went close to making it 2-0 as his curling shot went just off target.
Having threatened little up to that point, Sampdoria were then presented with the opportunity to draw level when the ball struck Emre Can's arm in the box and Valeri, after watching back the footage, pointed to the spot.
Quagliarella made no mistake with his effort from 12 yards as the veteran former Juventus striker registered his 10th goal in nine games.
The visitors then exerted some further pressure, before Dybala brought a diving save out of Audero and Giorgio Chiellini headed wide.
The start of the second half saw Juve goalkeeper Mattia Perin save a Gianluca Caprari shot and Audero then pull off a fine stop to keep out Blaise Matuidi's drive.
Matuidi headed wide soon after and Audero then kept out a Ronaldo effort before Juventus regained the lead, with VAR taking centre stage again.
On this occasion Valeri deemed Alex Ferrari to have been guilty of handball – a call that left Sampdoria seething – and Ronaldo stepped up to fire in his 14th league goal of the season.
Quagliarella subsequently shot over, Dybala sent a poor attempt wide and Ronaldo fired into Audero's arms.
Saponara then cracked a superb shot past Perin in added time, but his celebrations were cut short as Valeri reviewed the footage and chalked the effort off for offside.