Substitute striker Konstantin Vassiljev opened the scoring just past the hour soon after coming on with a strike from outside the area which Uruguay keeper Juan Castillo misjudged.
Estonia's second goal came four minutes later in the 65th when Vjatseslav Zahovaiko scored from Vassiljev's corner.
The Estonians used the match as a warm-up for Tuesday's Euro 2012 qualifier at home to Serbia. They are third in Group C with six points from four matches behind leaders Italy on 10 points and Slovenia with seven. Serbia are fifth with four points.
The first half was a dull affair with Uruguay striker Abel Hernandez unable to find a way through the home defence. The visitors, who lost to Germany in the third-place playoff at last year's World Cup, similarly snuffed out the Estonian attack.
The tempo picked up after the break with Estonia coach Tarmo Ruutli sending on Vassiljev who made the breakthrough before Zahovaiko wrapped up the victory for the home side.
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