Uruguayan striker Luis Suárez opened the scoring for Uruguay 10 minutes into the match as the Barcelona forward drilled a low free-kick past Igor Akinfeev, who was playing in his 109th match for Russia.
Uruguay went two up midway through the first half when Diego Laxalt's long-range effort deflected off Russia midfielder Denis Cheryshev and into the net.
During the match, Russia's right-back Igor Smolnikov received two yellow cards within nine minutes and was then sent off.
Previously, Russia qualified for the round of 16 after defeating Saudi Arabia 5-0 in the opening game of the tournament on June 14 and beating Egypt 3-1 last Tuesday.
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Uruguay, in its turn, defeated Egypt 1-0 in their opening game on June 15 and beat Saudi Arabia by the same scoreline on Tuesday, will face Russia on Monday in a match that will decide which of the teams wins Group A, while both have qualified for the round of 16.
The 2018 FIFA World Cup kicked off on June 14 and will continue until July 15, with the matches being played in 11 cities across Russia.
