Cavani had already put Uruguay in front early on, only for Pepe to head Portugal level in the 55th minute in a thrilling contest that was not the battle of attrition many predicted.
This has been his best World Cup in terms of goals scored, as he leaves with four in total, including a hat-trick in a 3-3 draw with Spain in the group stage.
Portugal hasn't reached the World Cup quarterfinals since 2006, when a young Ronaldo led the team to the semifinals and an eventual fourth-place finish.
The 31-year-old had a desperate day in front of goal as Uruguay eventually ground out a 1-0 win against Egypt to kick off their campaign in Russian Federation.
Portugal coach Fernando Santos threw up his hands in disgust, realising that coming from behind a second time against this Uruguay defence was going to be a tall order.
Thousands march in NYC to protest immigration policies
Spring St. after refusing to move out of the street when the Los Angeles Police Department declared an unlawful assembly. He also said his colleagues want to fix "this broken immigration policy ". "We're children of immigrants", she said.
The Atlético Madrid star has been involved in all four of France's games at the World Cup this summer, scoring in their first match against Australia and most recently in a thrilling win over Argentina, with both goals coming from the penalty spot.
Despite having just 39 per cent of the ball, the South Americans beat Cristiano Ronaldo's Portugal 2-1 on Saturday thanks to striker Edinson Cavani's two goals.
"He is an exceptional player", said Uruguay's veteran coach Oscar Tabarez. We know that the squares have been full back home and that the people there were really rooting for us. "I'm absolutely convinced that the national team will continue to be one of the best in the world".
"Certainly, yes, Cristiano still has a lot to give to football". It will be very hard for us.
And against Uruguay, they managed 61 percent ball possession, played more than double the number of passes of their opponent, and with a much better pass accuracy.
Cavani has three goals in this tournament and had 28 goals this past season for Paris Saint-Germain in league play, with another seven in Champions League matches.