Oscar Tabarez's side slumped to an embarrassing defeat, losing its first game ever in its Olympic history in the process, bringing an end to an 88-year unbeaten run
Both sides went into the game off the back of decent results in the opening group games, but it was Senegal which took the initiative in the 9th minute, with Moussa Konate tapping home a rebound from a corner.
They had a man sent off just after the half-hour mark, though, when Abdoulaye Ba barged over Luis Suarez, and was given his marching orders after being adjudged to have prevented a clear goalscoring opportunity.
Nevertheless, Konate struck again in the 37th minute, nodding home unmarked from a corner to expose Uruguay's vulnerability from set-pieces and despite and they were good value for their win.
Senegal made two changes to the side that managed to snatch a late draw against Team GB in its group opener, with Stephane Badji and Cheikhou Kouyate coming in for Ibrahima Balde and Idrissa Gueye.
Uruguay coach, Oscar Tabarez, made just the one change to his starting eleven, bringing in Nicolas Lodeiro, who struck the match-winner in its 2-1 victory over the United Arab Emirates, in place of Matias Aguirregaray.
Uruguay began the brighter of the two sides, with Gaston Ramirez striking a freekick from distance narrowly over in the second minute, but Senegal responded well with a decent spell of possession, gradually pushing its way up the pitch.
It went on to take the lead in the ninth minute through Konate, after he poked home from barely a yard out after Uruguay goalkeeper Martin Campana could only parry Kouyate's diving header at the back post from a Pape Souare corner.
But it didn't rest on its laurels, though, with Mane beating Ramon Arias for pace down the right-hand flank before cutting back an excellent ball for the unmarked Konate, who brought out a top save from Campana at his near post, tipping the ball acrobatically behind for a corner.
With Uruguay struggling to retain possession and create anything further forward, its best chance of the half came in the 27th minute when Ramirez struck an absolutely superb freekick from 30 yards out which struck the inside of the post before being hacked clear, with Mane rooted to the spot and well beaten.
The game was turned on its head moments later, when the already booked Ba was given a straight red card for a hugely cynical challenge after he barged over Suarez after a fine break away from a freekick up the other end of the pitch. Maximiliano Calzado volleyed well over after a goalmouth scramble from the resulting freekick.
Despite only having ten men, though, Senegal extended its lead in the 37th minute with Konate nodding in his second of the match and third of the tournament with the Uruguay defense tragically static, with Souare again credited with the assist, picking out the only green shirt in the entire six-yard box, amongst a sea of blue shirts.
With the half ending at a frantic pace, Cavani beat the offside trap in added time, picking up a sumptuously threaded through ball from Lodeiro, rounding the onrushing Mane, but not before Ciss got back in time and cleared his effort off the line as Senegal went in at the break two goals to the good but a man down.
La Celeste started the brighter of the two again in the second half, with Ramirez again threatening from range with a free-kick shortly after the restart. The Bologna man then set up an excellent chance for substitute Abel Hernandez, dinking a delightful ball over the back four, before the youngster saw his effort well blocked.
On the hour mark, Liverpool striker Suarez, who was enduring a bad afternoon at the office, nodded narrowly wide with the goal gaping after pealing off his marker at the back post, from a Lodeiro ball in, with Mane again in no man's land.
With chances few and far between after that, though, the game petered out into a scrappy affair, with both sides seemingly incapable of stringing more than two passes together, with only Suarez going close in the final stages after latching onto a Coates flick-on.
It brought an end to a deeply frustrating evening for the Uruguay side, as they failed to make the most of its numerical advantage and the chances that they did manage to create. Meanwhile, Senegal's physical approach appears to be paying dividends as they emerged deserved victors in a keenly-fought contest.
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