A first-half double from Giorgian de Arrascaeta was enough for Uruguay to win the game but they go out of the tournament after scoring a goal less than South Korea in the group stages.
The African side failed to avenge Uruguay knocking them out of the 2010 World Cup at the quarterfinal stage in a penalty shootout.
It was a fast start from both teams and Ghana were awarded a penalty following a VAR check after 18 minutes. Uruguay goalkeeper Rochet was adjudged to have brought down Mohammed Kudus inside the area.
Three minutes after the awarding of the spot-kick, Ayew stepped up and his weak penalty was easily saved by Rochet.
It brought back memories of Asamoah Gyan missing his penalty for Ghana with the last kick of the game in the 2010 World Cup quarterfinal game between the two nations.
Uruguay doubled their lead five minutes later through another De Arrascaeta strike following a fine team move.
The South American side looked comfortable after the quickfire double and wanted a penalty of their own before the hour mark.
Daniel Amartey made a clumsy challenge on Nunez inside the area but after another lengthy VAR check, the referee didn't award a penalty.
Ghana had chances late on but substitute Antoine Semenyo dragged his close-range effort wide while Kudus was denied by a fine save from Rochet.
As news filtered through of South Korea's result, Uruguay pushed to score one more goal but were denied and were eliminated from the tournament.