Liverpool's Darwin Nunez angered Ghana's players with his actions amid more World Cup controversy between the pair, but what he did seemed to work.
Ghana were awarded a penalty via VAR in the first half after Mohammed Kudus was felled by Uruguay goalkeeper Sergio Rochet.
After a lengthy check due to Kudus initially being given offside, referee Daniel Siebert overturned the offside decision and pointed to the spot.
The match is being played 12 years after Ghana and Uruguay met in the World Cup quarter-final of 2010, when forward Luis Suarez infamously handled Dominic Adiyiah's header on the goalline in extra-time, picking up a red card.
Suarez was then seen heading down the tunnel, and then celebrating wildly when Ghana's Asamoah Gyan struck his penalty against the top of the crossbar and over.
Uruguay then subsequently won the match on penalties, denying Ghana the honour of becoming the first African nation to reach the World Cup semi-finals.
At Qatar's Al Janoub Stadium it was Andre Ayew, the last surviving member of the Ghana side which lost in 2010, who stepped up to take the penalty, only for Rochet to spring to his left to save it.
However, the actions of Nunez may have made it harder for Ayew to score.
The Uruguay forward was seen scuffing the penalty spot in the immediate moments before Ayew's penalty, with several Ghana players spotting him and reacting angrily.
Referee Siebert also saw what Nunez did and issued him with a yellow card, but after the penalty was saved the Liverpool man could be seen screaming the German official, before a short time later he was challenged fiercely by Daniel Amartey.
Uruguay would soon race into a two-goal lead through a brace from Giorgian De Arrascaete.
Suarez spoke to media prior to the game at Uruguay's pre-match press conference, and refuse to apologise for the 2010 handball despite being referred to as "the devil himself" in the eyes of some in Ghana.
"I don't apologise about that, I took the handball, but Ghana player missed the penalty," said Suarez.
"I'd apologise if i injured a player or took a red card for this, but I took a red card (for the handball). It wasn't my fault because I didn't miss the penalty.
"You see the player who missed the penalty, he said he would do the same."
Ayew discussed the incident this week too, saying: "I'm the only one left in the squad from when that happened. Everyone knows how we felt. Everyone felt bad but, for me, I just want to get to the next stage at this World Cup," said this week.
"It's not about revenge. Whether it was, or not, we'll go with the same determination and same desire to win because we want to reach the next stage. I don't think Ghana has forgiven Luis Suarez. But for me, it's football. He took a decision. There's nothing to speak about."
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