Mercedes sealed its first win of the year at the Sao Paulo with a one-two win led by Russell - the winner of Saturday's sprint race - who finished ahead of his team mate Lewis Hamilton.
Both drivers adopted an identical two-stop strategy: soft tyres at the start, followed by a middle stint on medium and a final stint on soft.
"What an amazing feeling. A huge thank you to the whole team for making this possible. It's been an emotional rollercoaster, this season, this race. I felt in control, Lewis was super-fast and then when I saw the safety car, I thought this is going to be a difficult end," said Russell.
Lewis Hamilton fought back from being pushed off track by Max Verstappen in the early laps, coming from P8 to finish P2, just over one second behind his team-mate.
"What a result; huge congratulations to George who drove a perfect race - he looked so comfortable at the front and this will no doubt be first of many," said Andrew Shovlin, Mercedes Race Engineer. "Also a fantastic recovery for Lewis, we thought he'd have been out of the picture after the collision with Max but he put in a brilliant drive to get back to P2."
Ferrari driver Carlos Sainz completed the podium with a three-stopper, alternating between the medium and soft compounds.
"The team fought well for this result. We had a strong weekend and a solid race despite the penalty and some setbacks today, namely the issue with the tear-off that meant I had to pit earlier than planned and we had to rethink our strategy," said Sainz.
Both Ferrari drivers started on the Medium tyre, getting away well but overtaken by Lando Norris who was on Softs.
A Safety Car was required after a collision between Kevin Magnussen and Daniel Ricciardo, after which Charles set off to attack the Englishman, who clipped the F1-75, sending it into a spin. Leclerc had to pit for a new front wing and a set of tyres and rejoined last.
"It was a tough race today, the incident shortly after the start dropped me all the way to the back of the field. The pace and the feeling in the car were good and I'm satisfied with my performance and the recovery I made to finish P4," said Leclerc.
Sergio Perez started fourth but was passed during the final laps by both Ferraris, as well as Alpine's Fernando Alonso and his Red Bull team mate Max Verstappen, finishing the race in seventh on the medium tyres.
"It was a very good race for us today here in Sao Paulo. The car was very competitive and with our race strategy we were out of sync with most of the cars. Then, at the end, during the Safety Car period, I had newer tyres and we pushed as close to the front as we could; I overtook Sergio [Perez] and then I tried to look at Charles [Leclerc] but they were a step too fast for overtaking,"said Alonso.
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RESULTS
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Pos Driver Team Time Gap
1 Russell Mercedes 71 1h 38:34.044
2 Hamilton Mercedes 71 + 0:01.529
3 Sainz Ferrari 71 + 0:04.051
4 Leclerc Ferrari 71 + 0:08.441
5 Alonso Alpine 71 + 0:09.561
6 Verstappen Red Bull 71 + 0:10.056
7 Perez Red Bull 71 + 0:14.080
8 Ocon Alpine 71 + 0:18.690
9 Bottas Alfa Romeo 71 + 0:22.552
10 Stroll Aston Martin 71 + 0:23.552
11 Vettel Aston Martin 71 + 0:26.183
12 Zhou Alfa Romeo 71 + 0:29.325
13 Schumacher Haas 71 + 0:29.899
14 Gasly AlphaTauri 71 + 0:31.867
15 Albon Williams 71 + 0:36.016
16 Latifi Williams 71 + 0:37.038
17 Tsunoda AlphaTauri 70 + 1 Lap
Norris McLaren 50 Loss of Power
Magnussen Haas 0 Accident Damage
Ricciardo McLaren 0 Accident Damage