While Messi cut a forlorn figure during Argentina's 4-3 loss to France, Ronaldo tried to inspire.
The PSG man snuck in at the back post to dispatch Luis Suarez's pinpoint cross past Rui Patricio with just seven minutes on the clock.
The European champions equalised when Pepe headed home following a short corner, but Uruguay swept up the field and carved them open once more, with Cavani firing home his second and Portugal unable to respond.
After almost five and a half hours of football, it was the first goal Uruguay had let in at this World Cup - indeed it was the first they had conceded in 2018.
The Paris Saint-Germain striker was in visible pain near the 70-minute mark when he went down holding his calf, and moments later when Cristiano Ronaldo helped him walk off the field to receive treatment.
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The Opec oil producers' group agreed to increase output, as did Russian Federation , but this failed to reassure markets. The official Saudi Press Agency confirmed a phone call between the two leaders about oil, but mentioned no specifics.
After huffing and puffing his way through the opening two group matches, Uruguay's talisman Edinson Cavani has finally arrived at the party, and in some style.
In planning the match, focusing on our opponent and considering the level that every player has, what Ronaldo has on top of all of these qualities is that he is the leader of that team. I don't have words to describe it.
Oscar Tabarez will be sweating on the fitness of his match-winner as he hobbled off the pitch with 15 minutes to play, as they gear up to face France in the quarter finals.
"I hope it is nothing and I can keep going", he said. "But you always want to win, and we lost, so well done to Uruguay for making it through". "Usually we also score".
Santos' side dominated the match for large portions but were defeated by two excellent goals from Uruguay talisman Edinson Cavani either side of Pepe's equaliser.
Sanchez hopes Lukaku wins World Cup Golden Boot
The route we've got now is Colombia , who have been poor and had James Rodriguez limped out of the Senegal game. First of all, Colombia will be really tough opponents, but they have a few things going for them.
Diego Godin and Jose Gimenez will start in central defence and they will count on all their La Liga experience at Atletico Madrid to stop arch-rival Ronaldo in his tracks.
But parity did not last long, Cavani steering a brilliant curling finish into the corner after 62 minutes following Bentancur's beautifully-weighted pass into his path.
Uruguay set up perfectly to stop him from being the difference maker that he so often is in matches, especially in big matches such as this.
Attention will now turn to whether Ronaldo will continue to captain Portugal but the 33-year-old stated that those questions are for another day.
Casey leads Travelers by four after firing 62
Halfway leader Brian Harman (69) slipped back into a tie for third at 11 under with Anirban Lahiri of India (65) and American J.B. Casey, who shot 65, 67 and 62 to lead the field by four shots coming into Sunday, birdied his opening hole.
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