Giovanni Trapattoni's side will play the South Americans at the Aviva Stadium in Dublin on 29 March, three days after the Republic take on Macedonia in a UEFA EURO 2012 qualifier at the same venue.
Trapattoni said: "After playing Brazil and Argentina this year, we now welcome another strong South American side.
"Having watched Uruguay in this summer's World Cup, I was impressed by their performance, particularly against Holland in the semi-final, when they were narrowly beaten. This game will act as further good preparation for the June qualifier, before our return leg against Macedonia."
Ireland opened their qualifying campaign with victory over Armenia in Yerevan and then a home win over Andorra earlier this month.