Ronaldo became just the second men's player to a century of strikes for his country as he netted a stunning free-kick late in the first half in Stockholm on Tuesday.
That effort came after Gustav Svensson was sent off for the home side, who never threatened to rescue a result, with Ronaldo instead adding another wonderful goal after the break.
Fernando Santos' men survived an early scare as Marcus Berg wastefully skewed a header wide, although the visitors were similarly profligate as Pepe failed to turn in a glorious cross from Bernardo Silva, who was injured in the process.
Ronaldo was twice then denied his milestone goal as Robin Olsen made a pair of instinctive stops with his legs, blocking a snapshot on the turn before diverting a powerful one-on-one blast onto the crossbar and over.
But the game was taken away from Sweden on the brink of half-time as Svensson, already booked, lunged in recklessly on Joao Moutinho and was shown a second yellow card.
Ronaldo dispatched the subsequent free-kick into the top-left corner to finally bring up his ton after a near 10-month wait.
Portugal toiled in pursuit of a second and Bruno Fernandes prodded against the bar, so it was predictably left to Ronaldo to make the points safe, his 101st goal at this level a beautiful effort curled over Olsen into the top-right corner.
Joao Felix might have added his name to the scoresheet in the closing stages but could not stretch to reach Fernandes' low ball and then found Olsen his equal.
What does it mean? Holders off to a flier
Portugal were aided by the red card here, but the defending Nations League champions are quickly making their mark in this competition once again.
They have two wins from two and, even with France still to play home and away, they show no signs of slowing - nor does their 35-year-old goalscorer...
Ronaldo record in sight
Having sat out of the Croatia game, meaning his tally of 99 goals had not improved since November 2019, Ronaldo was evidently determined to get on the scoresheet.
Olsen twice got the better of the Juventus talisman, but a pair of stunning strikes were fully deserved and he can now look towards the global record of 109 international goals, held by Iran great Ali Daei.
57 & 10 - Cristiano Ronaldo's landmark goal for Portugal was scored via a direct-free kick; it was the 57th time in his career that he has scored in this manner, and the 10th for Portugal. Incredible. https://t.co/0ztGeknzNU— OptaJoe (@OptaJoe) September 8, 2020
Svensson sinks Swedes
The villain was as obvious as the hero in Stockholm. Sweden were clinging on even before Svensson's foolish red card.
The Seattle Sounders midfielder should have known better than to dive in when on a booking, yet his attempted challenge was so strong and so late he might have earned a straight red if not for his earlier card.