The two-time World Cup winners twice came back from a goal down before the Palermo striker finished off the Europeans
Ukraine found the net 15 seconds into the contest thanks to Andriy Yarmolenko but could not hold off Uruguay as goals by Alvaro Gonzalez, Diego Lugano and Abel Hernandez saw the Copa America winners earn a 3-2 victory at Metalist Stadium in Kharkiv.
Hernandez, who came on in the second half, found the net in the 87th minute off of a wonderful through pass from Luis Suarez, taking a touch past Olexandr Shovkovskiy before knocking the ball home with ease, earning another victory for Oscar Tabarez's side.
Yevhen Konoplyanka helped the Euro 2012 co-hosts get the early lead when he stole the ball from Uruguay in the middle of the pitch, finding Marko Devic, who was darting towards the box. The striker marched forward before slipping a low pass in front of the net to Yarmolenko, who placed his shot with class to the right of a diving Fernando Muslera, sending the fans into a frenzy before many even took their seats.
In the ensuing minutes, the teams split possession, but neither side's attackers could threaten the opposing goalkeeper.
The hosts looked to play the ball towards the touchline, opening up space in the middle to go on the attack. It was successful time after time as the boys in yellow engineered several spurts of brilliance to infiltrate the Uruguayan penalty area, keeping them on their heels. However, they could not find their second goal before Gonzalez's strike.
The Lazio man levelled the score a just before the break with a shot from 20 metres that Shovkovskiy should have handled without any problems. However, the ball hit off his arm and bounced into the net.
With the 1-1 scoreline looking certain heading into the break, the Ukrainians regained the lead just seconds later.
Yarmolenko sent in a low cross into the middle of the box between numerous players from both teams, finding Konoplyanka, who only needed one touch on the ball with the inside of his right foot to knock it off the crossbar and down into the goal, leaving Muslera with no chance of stopping it.
Easily the better side in the first half, Ukraine looked to continue their quality play in the second while holding on to the advantage.
But Lugano would have nothing of it, bringing his nation back early in the second half off a set piece, flicking on Luis Suarez's free-kick with a soft touch to the back post before Hernandez left it late as the South Americans picked up where they left off their triumphant 2011 Copa America campaign.