Edinson Cavani's early opener from a superb Luis Suarez cross put La Celeste in the driving seat, enabling them to sit back and soak up the Portuguese pressure.
The European champions huffed and puffed but could not blow down the Uruguayan house, searching in vain for a moment of magic from Cristiano Ronaldo, who passed up a presentable chance from a dangerously positioned free-kick.
It was from another sort of dead-ball delivery that Portugal found a chink in the armour, Pepe equalising with a header from a corner after the break, FIFA.com reported.
However, the veteran centre-back's joy was short-lived, as Cavani restored the South Americans' lead with a stunning side-footed finish not long afterwards.
The Uruguayans will have to be just as solid at the back if they are to emerge victorious from their quarter-final tie against France, who were scintillating going forward during their win over Argentina earlier in the day. The stage is set for a cracker in Nizhny Novgorod on 6 July.
