Uruguay's Jose Gimenez headed in a free-kick in the 89th minute to seal a 1-0 win over Egypt in their World Cup Group A clash on Friday.
Egypt forward Mohamed Salah was left on the bench despite coach Hector Cuper saying he was fit to play following the shoulder injury sustained for Liverpool in the Champions League final last month.
The North Africans battled hard but Uruguay had the best of the chances with Luis Suarez missing a couple of decent opportunities and Edinson Cavani hitting the post with a free-kick.
But Gimenez finally made the breakthrough to put Uruguay second in the group behind hosts Russia, who battered Saudi Arabia 5-0 in the tournament and group opener on Thursday.
Salah's omission came as a big surprise and he went unused despite Egypt putting on three substitutes.
Goalkeeper Essam El Hadary, who would be the oldest player to feature in a World Cup at 45-years-and-5-months-old, was also only named as an Egypt substitute and did not enter the fray.
Mahmoud Hassan had a half chance for Egypt after just over 10 minutes in Yekaterinburg, the eastern-most Russian city hosting games at this World Cup.
Suarez then fired wide for Uruguay soon after and had a better opportunity midway though the first half when he dragged a close-range shot beyond the post.
The Barcelona forward then forced a decent save from Mohamed El Shenawy shortly after the break.
Egypt's Ahmed Fathi later tried his luck from distance before Suarez wasted another good chance after he finally linked up well with strike partner Cavani following fitful interaction.
Cavani then rattled the post and it looked like it would not be twice champions Uruguay's day until Gimenez rose to power home late on.
Despite the loss, Egypt - in their first World Cup for 28 years - matched their opponents for large spells and defended stoutly.
Another negative for Egypt was the sight of Tarek Ahmed limping off, adding to their injury problems.
Many empty seats were scattered across the Soviet-era stadium, which was reconstructed for the tournament by adding two huge temporary stands behind each goal.
For the second straight game there was no need for the Video Assistant Referee System, which is making its World Cup debut.
