Otto Addo's men currently sit second in the section behind Portugal and will be guaranteed to progress to the last 16 if they win, and a draw would also be enough if South Korea cannot beat Portugal by at least two goals.
Meanwhile, the South Americans sit bottom with one point after a disastrous start and simply have to find a way to win to stand any chance of advancing to the knockout rounds.
Ghana and Uruguay have only ever met once before in any competition, but it was one of the most memorable World Cup matches in recent memory, as La Celeste prevailed on penalties in the 2010 quarter-finals.
Before controversy reared its ugly head, Sulley Muntari's long-range stunner and Diego Forlan's free kick lit up the FNB-Stadium in South Africa, and the final minute of extra time still lingers long in the memory of the African nation.
With Dominic Adiyiah's header soaring towards goal, Luis Suarez channelled his inner goalkeeper to parry the ball away and was sent off for his troubles, but he stayed on the sidelines long enough to see Asamoah Gyan's penalty hit the woodwork.
Adiyiah's luck was not in on the day, as the Ghana attacker then saw his penalty saved in the shootout by Fernando Muslera as Uruguay advanced, with Suarez potentially single-handedly - or quite literally, double-handedly - denying the Black Stars the chance to become the first African nation to reach the World Cup semi-finals.
Gyan admitted after the game that Suarez's actions would be labelled as heroic, and the fire within the Ghanaian bellies will be burning bright as they seek to eliminate Uruguay from the 2022 tournament and give themselves another shot at knockout glory.
GHANA VS. URUGUAY HEAD-TO-HEAD RECORD
Ghana wins: 0
Uruguay wins: 1
Draws: 0
Ghana goals: 1
Uruguay goals: 1
MATCH HISTORY
July 2, 2010: Uruguay 1-1 Ghana [a.e.t, Uruguay win 4-2 on penalties] (World Cup)
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