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Uruguay went into Friday's game without key striker Edinson Cavani, who was ruled out with a calf injury, with Cristhian Stuani drafted into the starting line-up.
The impact on their attack was noticeable. Without Cavani, who scored twice in the round of 16 win against Portugal, Uruguay's moves forward lacked a focal point, and Luis Suarez found less space and openings against a well-drilled French defence.
The South Americans battled but their talented generation of players, including the defensive rock Diego Godin, look like ending their international careers without the World Cup success they have threatened to deliver. "I'm proud of my team mates - they were lions," said skipper Godin.
"We are a team where everyone gives everything in the matches and in preparation..I just have words of gratitude for my team mates," he said.
France rarely sparkled, but they didn't need to move through too many gears, and they go into the semi-finals without any major weak points and appearing capable of taking on anyone of the survivors in this tournament.
"I think we deserve the result," said coach Didier Deschamps, a World Cup winner with France in 1998.
"We were better than they were today. We had far more mastery, especially in the second half. We didn't want to give them any opportunity. The attitude is there but we have margin for improvement," he added.
France forward Kylian Mbappe, who had ripped apart Argentina in the previous round with his directness and pace, wasted a good opportunity to open the scoring in the 15th minute when Olivier Giroud headed across the box to him but the 19-year-old's looping header was off-target.
A relatively quiet game burst into life in the 40th minute when Varane sprinted clear of his marker to meet a well-placed Griezmann free kick with a perfectly angled header.
Moments later, France goalkeeper Hugo Lloris ensured his side went in at the break with the advantage, producing a brilliant one-handed save to keep out a Martin Caceres header although Diego Godin will be disappointed his follow-up shot was wildly off target.
If that was an example of goalkeeping at its very best, Uruguay's Fernando Muslera showed how easily it can go wrong for the custodian with a horrendous error to gift France their second goal in the 61st minute.
Griezmann tried his luck with an effort from outside the box which was straight at Muslera, but the keeper's ill-chosen attempt to palm the ball away ended with him merely deflecting it into the net.
It was a mistake that left Oscar Tabarez's team with too much to do to turn the match around.
"Fernando is a great goalkeeper... We all make mistakes.. On other occasions, he has rescued us with incredible saves," said Godin.
Mbappe then caused a melee after he went down claiming he had been struck in an incident off the ball and was confronted by a furious Godin about his playacting.
That proved to be the last hint of any drama in what was overall a disappointing game which had promised much more.
In Friday's other match, Belgium struck early and held off a late Brazil fightback to send the five-times champions tumbling out of the tournament with a 2-1 victory in an end-to-end thriller.
A Fernandinho own goal and a brilliant Kevin De Bruyne strike gave Belgium a spot in the last four.
Saturday's quarter-finals see England take on Sweden and hosts Russia face Croatia.