Having rescued their unbeaten start to the league season with the equaliser against Atalanta last time out, Ronaldo struck in each half to secure a 17th win in 19 games heading into the mid-season break.
Sampdoria, who had levelled through Fabio Quagliarella's penalty and had an injury-time Riccardo Saponara strike disallowed by VAR, have now lost their last four away league games against Juve for the first time since 1968.
The only negative for Juve was the loss of goalkeeper Wojciech Szczesny to an apparent injury in the warm-up.
Samp's resistance lasted less than two minutes, Ronaldo gathering Paulo Dybala's pass, cutting inside and firing right-footed through the grasp of Emil Audero.
Juve seemed to relax after going ahead, though, and Samp levelled after 32 minutes through Quagliarella's spot-kick after a VAR review led to Emre Can being penalised for the ball striking his elbow.
Audero denied Ronaldo with a flying save as Juve stepped up the pressure after the break, but he could do nothing to stop the Portugal star from burying a penalty past him 65 minutes in, after Alex Ferrari was deemed to have handled in the box.
Saponara thought he had struck a sublime equaliser in injury time after a mistake by Mattia Perin, but a VAR check showed he was offside in the build-up, sparing the Juve keeper's blushes.
Juve end 2018 in ominous form
Unbeaten after 19 matches and with a new Serie A record of 53 points at this stage of the season, Juve are looking almost unstoppable heading into the mid-season break.
Even if Napoli beat Bologna later on Saturday, they will be nine points behind the champions when league duties resume next month.
Sampdoria, meanwhile, could be five points adrift of the top four if Lazio defeat Torino.
Ronaldo rescues Juve again
Fresh from his crucial cameo against Atalanta, Ronaldo took his tally for the season to 14 strikes in Serie A, and ensured Juve broke the 100-goal mark for the calendar year. A little more than a month away from his 34th birthday, he looks as decisive as ever.
