Sergio Perez took the chequered flag on a remarkable evening in Bahrain to secure the first victory of his career ahead of Renault's Esteban Ocon and Racing Point team-mate Lance Stroll.
Russell, promoted to the fastest Formula One machine in history after Lewis Hamilton contracted coronavirus, was hunting down Perez and trailed the Mexican by just two seconds before he was forced to stop for new rubber.
Only moments earlier, Russell, a 3000-1 outsider to win here in the desert before Hamilton was sidelined for the first time in his 256-race career, dropped down the order following a Mercedes pit-stop howler.
The 22-year-old held a commanding five-second lead over team-mate Valtteri Bottas when Mercedes called both of their drivers in for new rubber after a safety car was deployed following a spin by rookie Jack Aitken.
But there was a mix-up among the Mercedes mechanics as they mistakenly put Bottas' tyres on Russell's car. That meant Russell had to come into the pits again on the following lap dropping him to fifth.
"You should now have a tyre advantage," Russell's race engineer for the weekend, Pete Bonnington told the young Briton. "I f*****g hope so," Russell replied.
The safety car pulled in with 19 of the 87 laps remaining and Russell – with the bit between his teeth – wasted no time in moving up the order, passing Bottas, Lance Stroll and Esteban Ocon inside two laps.
He set about chasing Perez, taking more than one second out of the Racing Point man's lead before his puncture. It allowed Perez to cruise to a 10-second victory with Russell eventually crossing the line in ninth.
Russell first discovered he could be replacing Hamilton for the penultimate round of the year following a 2am bathroom phone call with Mercedes team principal Toto Wolff on Tuesday.
And after topping both practice sessions on Friday, before missing out on pole to Bottas by just 0.026 seconds, Russell then led the majority of the race and appeared on course to become only the fourth British driver to win this century.
Russell exploded off the start-line, flying past pole-sitter Valtteri Bottas with ease to take the lead on the run down to turn one. Indeed, after Ferrari's Charles Leclerc crashed into Perez and Red Bull driver Max Verstappen smashed into the tyre barrier as he attempted to avoid the two cars, Russell's first-lap lead over Bottas stood at three seconds.
The safety car was deployed but when the racing resumed on lap seven, Russell remained in control, and after both Mercedes cars stopped for their scheduled one pit-stop, he had established an eight-second margin over Bottas.
But the race turned on its head on lap 63 of 87 when the safety car was deployed for a second time after Aitken hit the barriers.
Undeterred by his temporary team’s pit-stop error, Russell looked likely to put the pressure on Perez in the closing stages before his puncture.
McLaren driver Carlos Sainz finished fourth ahead of Renault's Daniel Ricciardo with Bottas eighth.
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