Ruben Amorim's side have won their last two in the competition and are third straight victory could see them join the top eight.
United are currently 12th, which is four places outside the automatic knockout round qualification places.
The Red Devils head into this important game off the back of a disappointing home defeat to Nottingham Forest in the league.
So, they will need to put that behind them and get back to winning ways to boost their chances of qualification.
Viktoria Plzen vs Man United: How to follow
This Europa League clash will take place on Thursday, December 12.
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Kick-off at the Doosan Arena is scheduled for 5:45pm.
Man United are taking part in an earlier kick-off simply due to scheduling and TV decisions.
talkSPORT 2 will have live coverage from the Czech Republic, with commentary coming from Alex Crook and Scott Minto.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream.
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You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
The game will be broadcast live on TNT Sports from 5:30pm too.
Viktoria Plzen have lost both of their previous European games against English sides, going down 3-0 at home and 4-2 away to Manchester City in the 2013-14 UEFA Champions League.
Manchester United have never won away against Czech opposition before (D2 L1), with this their first such visit since a 0-0 draw at Sparta Prague in October 2004.
Viktoria Plzen vs Man United: Team news
United are missing a couple of defenders for this game.
Luke Shaw hasn't travelled as he'll be out for a prolonged period after suffering yet another injury last week.
Jonny Evans has also stayed at home, but Leny Yoro is fully fit and after making his debut at the weekend, he will be part of the team.
Youngster Toby Collyer is part of the travelling squad too, providing some back-up to a strong collection of midfielders.
Marcus Rashford will be pushing for a start after back-to-back benchings in the Premier League.
Joshua Zirkzee could also get some minutes to try and prove why he should start over Rasmus Hojlund up front.
Manchester United are unbeaten in their five UEFA Europa League games this season (W2 D3), last opening up a campaign of major European football by going six without loss in 2013-14 in the UEFA Champions League.
Rasmus Højlund has scored eight major European goals for Manchester United and could become the third player to net nine such goals for the Red Devils while aged 21 or younger after Marcus Rashford and Wayne Rooney (9 each).
Viktoria Plzen vs Man United: What has been said?
United's sporting director, Dan Ashworth, left his post over the weekend in what was an unexpected departure.
However, talkSPORT's Simon Jordan believes it was the correct decision by the club to mutually part ways.
Former Crystal Palace owner Jordan said earlier this week: "It's better to find out now that you don't have the synergy you thought you had.
"Maybe he's going to Arsenal? Maybe they've got a sporting director vacancy?
"The bottom line is, they spent a couple of million quid to get him out of his contract with Newcastle, but they spent £35million on Donny van Beek and then sold for £500,000, people will make decisions that you don't think they're going to be.
Simon Jordan reveals why he backs Manchester United's sacking of Dan Ashworth
"Better to find it out quick, if you're going to get to it, get to it fast.
"If you don't think someone has got the chops or the relationship isn't right, then make the decision and make it quick."
He added: "The bottom line is you've got personalities there, and you've got marginal gains, which obviously has some input in there.
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"I mean, look, they needed to own their decisions. His fingerprints were all over Erik ten Hag.
"So I don't think it's a particular glowing endorsement."
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