Ronaldo has scored four times in Russian Federation but Portugal have already shown that they can win without him - they beat France in the Euro 2016 final despite losing the Real Madrid man to injury early on.
And after Portugal equalised on Pepe's header in the 55th minute, it was Cavani again finishing a ideal Uruguay counter in the 62nd with a shot from just inside the penalty area that caught Portugal goalkeeper Rui Patricio slightly out of position and curled inside the far post.
But by defeating the reigning European champions, the two-time World Cup winners will face France in Nizhny Novgorod on Friday with hopes of making it to the semifinals and keeping alive the prospect of an all-South American clash in the final. The Uruguayans will look towards their attacking duo of Edison Cavani and Luis Suarez to provide their firepower, while Diego Godin leads from the back.
How Godin and Gimenez fare against Ronaldo is one of the intriguing subplots surrounding this fixture, though both sides' defensive records have some fearing a tiresome contest.
Cavani and Luis Suarez unlocked the Portuguese defense early with two incredible cross-field passes.
The goal was the first conceded by Uruguay since November but they were back in front within seven minutes as Cavani produced a sublime finish. He required assistance to make it off the field, provided by Ronaldo, who aided his opponent all the way to the touchline.
Ronaldo was involved somewhat in Portugal's goal, even if he didn't come close to getting a touch on the cross.
The goal opened up Uruguay who, notoriously cagey throughout the tournament, pressed forward, sensing that a Portugal defense that had leaked five goals in four games could crack again.
With four goals from his first three games, the Real Madrid star has been living up to his pre-tournament hype. KEYS TO THE GAME Stopping Ronaldo.
"We have to be strong as a team, as strong as Uruguay".
Defender Jose Gimenez is set for a return for Uruguay after missing the victory over Russian Federation with a back injury.
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.
Not long after the restart, Portugal found their breakthrough when Cavani's earlier leap was mimicked by Pepe in the 55th minute when he rose unmarked to meet a cross into the box and power a header past a rooted Muslera.