United had gone behind just three minutes after the break thanks to another Andre Onana howler.
Manchester United came back to beat Viktoria Plzen
But after coming on as a 56th-minute sub, Hojlund scored in the 62nd and 88th to give the Red Devils their first away win in Europe since March 2023.
Hojlund's Premier League record may not be one to shout about for United but he loves it in Europe.
This pair makes it 10 goals in 12 appearances, plus an assist.
It lifted some of the gloom hanging over the club and also means they have a foot in the next stage of the Europa League.
Things changed after a raft of substitutions early in the second half for United, which gave them a much-needed confidence boost ahead of Sunday's derby at The Etihad.
Hojlund has to start that one, Joshua Zirkzee will need to stay on the bench and was rightly hooked a minute before United had equalised.
Zirkzee was certainly doing himself few favours once again here in the Doosan Arena.
For every decent piece of work there are at least two glaring first touches that immediately give possession back to the opposition.
He certainly wasn't having any chances on goal in the first period.
United have been a hard watch at the moment and the first half in minus three degrees here in Plzen was taking it to another level.
The 640 loyal followers from Manchester in one corner of the ground must have been longing for a warm fire at their local.
Still they come and they were rewarded with that second-half comeback.
In the first period United didn't look in particular danger but then again didn't look dangerous either.
It looked like being that sort of game.
The only effort of note before the break came from captain Bruno Fernandes, who, with Amad Diallo, was the only player worthy of some praise before the break.
Casemiro played the ball out from the back to Zirkzee who for once found his man in Fernandes and he charged forward before having a shot towards the far bottom corner.
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