Russia's impressive progression to the last 16 has provided one of the tournament's major surprises so far, but Stanislav Cherchesov's side were brought back down to earth in a sweltering Samara.
In a fast start, Uruguay were ahead inside 10 minutes as Suarez, who scored the winner against Saudi Arabia on matchday two, found the net with a pinpoint free-kick.
Denis Cheryshev's own goal compounded Russia's misery 13 minutes later, with Smolnikov's dismissal – for a second yellow card issued after a foul on Edinson Cavani prior to half time - all but ending hopes of a comeback.
Russia showed greater solidity after the interval, with Artem Dzyuba wasting a chance for a consolation, but the damage was already done by the time Cavani got his first goal of the tournament in the 90th minute.
Portugal and Spain - who face Iran and already eliminated Morocco respectively later on Monday - are likely to await these sides in the knockout stages, with Uruguay's victory meaning they will face the side who finish second in Group B.
7 - Luis Suárez has now scored seven goals for Uruguay at the World Cup; only Oscar Miguez (8) has netted more in the competition for La Celeste. Finisher. #URURUS #URU #WorldCup pic.twitter.com/3WWXcSAied— OptaJoe (@OptaJoe) June 25, 2018
Oscar Tabarez's side had already threatened before taking the lead when Suarez curled a low free-kick into the bottom-right corner after Yuri Gazinskiy's desperate foul on Rodrigo Bentancur.
Cheryshev looked set to continue his fine form as Russia responded in force, only for the Villarreal winger to hammer a half-volley straight at Fernando Muslera on the goalkeeper's 100th Uruguay cap.
Russia's leading scorer would find the net at the other end on 23 minutes, though, as his touch diverted Diego Laxalt's first-time effort past Igor Akinfeev.
Uruguay would have had a third soon after if not for a fine save from Akinfeev, who prevented Bentancur celebrating his 21st birthday with a goal.
Matters were made worse for Russia in the 36th minute, Smolnikov picking up his second booking after lunging in on Cavani, just eight minutes after being carded for a foul on Matias Vecino.
Despite their numerical disadvantage, Russia were not reluctant in coming forward following the restart, a promising move breaking down when Mario Fernandes failed to tee up Aleksey Miranchuk in the area.
Cavani could have added a third just after the hour, but the Paris Saint-Germain striker elected to go down under pressure from Sergei Ignashevich rather than get a shot off, failing to fool referee Malang Diedhiou.
Muslera almost ruined a third successive clean sheet when his sloppy pass enabled Russia to counter, though Dzyuba sent his close-range effort well wide.
Uruguay's front man would have his goal in the final minute of normal time, though, Cavani thumping home the rebound after Akinfeev had done well to keep out Diego Godin's header as Uruguay cruised to maximum points from their three games.
2 - Edinson Cavani is the second player to score in three separate World Cup tournaments for Uruguay (2010, 2014 and 2018), alongside his strike partner Luis Suárez. Duo. #URURUS #URU #WorldCup pic.twitter.com/YY95W0RLo0— OptaJoe (@OptaJoe) June 25, 2018
Key Opta Facts:
- Uruguay have finished as first round group winners for just the fifth time, having done so previously in 1930, 1950, 1954 and most recently in 2010.
- Russia are the first European side to fail to top their group as the host nation since Spain in 1982.
- Uruguay are the first side to win all three of their group games without conceding a single goal since Argentina in 1998 (seven goals scored, none conceded).
- Russia are now winless in each of their six World Cup matches in which they have conceded the first goal (D1 L5).
- Denis Cheryshev scored the sixth own goal at this year's tournament, the joint-most number of own goals at a single World Cup (also six in 1998).
- Uruguay striker Luis Suarez is now his country’s second outright top goalscorer at the World Cup with seven goals, only Oscar Miguez (8) has netted more.
- Edinson Cavani became just the second player to score a goal in three separate World Cup tournaments for Uruguay (2010, 2014 and 2018) after his strike partner Suarez.