Luis Suarez grabbed his second goal of the tournament to open Uruguay's account with a free kick after 10 minutes and they doubled the lead with an own goal from Russia's Denis Cheryshev soon afterwards.
That silenced a vociferous home crowd which had been in party mode after Russia's opening two victories and were not expecting their final group contest to be effectively ended in the 36th minute when Igor Smolnikov was sent off.
Edinson Cavani bundled home a third goal for Uruguay at the death to wrap up their third straight victory, ensuring they finished above the Russians, who will now have to face the winners of Group B in the last 16.
Uruguay, who kept their sixth straight clean sheet, will face the runners-up from Group B, which will be decided when Spain, Portugal and Iran battle it out for two last-16 spots later on Monday.
While Russia had confounded those who predicted a group stage exit with resounding victories over Saudi Arabia and Egypt, there was still a question mark over how they would perform when they faced stronger opposition.
Twice World Cup winners Uruguay offered them the chance to show they truly belonged among the elite, but it was an opportunity wasted, merely serving to give ammunition to the doubters.
"I believe that when we had 10 people in the pitch, we were running and wanted to attack more," said Russia coach Stanislav Cherchesov.
Yet while Smolnikov's sending off may have ended Russia's hopes of a third win, in truth the encounter had already swung decisively against them.
They went behind in sweltering conditions at the Samara Arena when Suarez struck a low free kick into the bottom corner that should have been easy pickings for Russia keeper Igor Akinfeev.
Sadly for the home fans, who had created a deafening din in the opening minutes, Akinfeev inexplicably vacated his bottom left corner, moving back to the side of the goal his wall was guarding and leaving space for Suarez to stroke the ball home.
CHERYSHEV DEFLECTION
It was Suarez's second goal of the tournament and seventh World Cup goal overall for Uruguay, with only Oscar Miguez having scored more for the South Americans with eight.
Uruguay doubled their lead in the 23rd minute when Diego Laxalt's shot from the edge of the area deflected off Cheryshev, leaving Akinfeev wrong-footed.
With qualification already assured, Cherchesov had made three changes to his starting line-up with Smolnikov among those drafted in.
It was a decision the coach may have come to regret when any hope of a Russian revival was extinguished with the defender's red card, given after a clumsy late tackle on Laxalt brought a second caution.
With their work done, Uruguay took their foot off the pedal in the second half and only added to their lead in the 90th minute when Cavani finished from close range after Diego Godin's header was saved.
Russia battled valiantly and had a penalty appeal turned down after a VAR consultation late in the game, but there was little else to cheer the home fans.
For Uruguay's demanding coach Oscar Tabarez, whose side had not hit top gear in their previous two matches, it was a case of job done - even if there was certainly no cause for celebration.
"We could have won by more goals, we lack experience so we didn't score on some counter-attacks when we should have," he said. "We need to improve and do it soon."
(Reporting by Toby Davis, editing by Nick Mulvenney and Pritha Sarkar)
