Seven-time F1® champion Hamilton has been ruled out of the penultimate race of the 2020 season after testing positive for coronavirus on Monday.
Mercedes reserve drivers Vandoorne and Esteban Gutierrez seemed natural fits to stand in for Hamilton, but the seat instead went to Russell, with Williams agreeing to release the 22-year-old Briton.
Vandoorne, who flew to Bahrain on Tuesday to provide cover for Hamilton, took to social media to air his displeasure but says he respects the Silver Arrows' decision.
"Firstly, I want to wish Lewis Hamilton a speedy recovery and hopefully he'll be back in the car asap! Nobody can really replace him!" he posted in a statement on social media.
"Obviously, I'm disappointed not to get the chance to drive for Mercedes this weekend. After having spent the year travelling to all F1® races and dedicating so much time, physical training, commitment to this programme… it hurts!
"On the other hand, I respect the choice of putting George Russell in the car. He has been one of the standout drivers and he fully deserves this opportunity.
"It's moments like these that make my drive even bigger and I can assure you I'm going to continue giving 100 per cent."
Some have suggested Mercedes development driver Russell is effectively auditioning for a Silver Arrows seat in 2022, but he is unconcerned by that talk.
"There have been no targets expected of me by Mercedes because you can't judge somebody off one race," he said. "It's not in the back of my mind. I'm going to go out there, enjoy it and learn as much as I can.
"I have a job to do on my return to Williams and try and push that team forward. I need to take this opportunity with both hands and maximise the learning.
"The future will be judged over the course of a season, and what's happened in the past, not just one or maybe two races."
Russell will team up with Valtteri Bottas, who is the favourite to win his third race of the season in Hamilton's absence.
Bottas, who has only finished higher than eighth in two of the past five races, is determined to succeed in Bahrain.
"For me, it's a great motivation to have a new team-mate," he told Sky F1. "Obviously I'll try to be ahead of him and win the race, that's the only thing on my mind.
"Being a part of the team for a few years, obviously everyone would expect me to be on pole and win the race. That's my goal.
"I'll try to end this season on a positive note. I'll try to make the most out of it and hopefully that can help me for the future.
"I'm sure this young, hungry guy will give it all he's got. He's a talented guy and he's super excited to be in the team."
But Bottas, under contract with Mercedes until the end of next season, acknowledged there is some added pressure to finish ahead of his temporary team-mate.
"If he beats me, for sure it wouldn't look so good on me if I had a normal race fair and square, so I try to avoid that," he said.
"But I'm not a person who thinks like that. I try to turn things into motivation and positive thinking and that's my mindset for this weekend."