The result has left the Red Devils in fifth spot in the Europa League table, two points ahead of ninth-placed Lyon, while Plzen are 15th, also boasting 10 points from their opening six matches of this season's competition.
There were some nervy moments for Man United goalkeeper Andre Onana early on, with high balls into the away side's penalty box causing problems, which has been the case in the early stages of Ruben Amorim's time at the helm.
Bruno Fernandes forced an excellent save from Plzen goalkeeper Martin Jedlicka in the 31st minute, with the Red Devils captain driving one from distance, and that proved to be the closest that either side came in the opening half of action, which was uneventful for long periods.
The structure from a defensive point of view was much-improved, but Man United were struggling in the final third of the field, with Marcus Rashford, Joshua Zirkzee and Amad Diallo all finding it difficult to make their mark.
Plzen took the lead early in the second period following a huge mistake from Onana, who gave the ball away to Pavel Sulc inside the Man United box, and the attacker squared for Matej Vydra to fire into the back of the net.
The pass into Matthijs de Ligt was never on, but Onana attempted to force it and paid the ultimate price.
Man United were back on terms in the 62nd minute, as substitute Hojlund converted from close range after a strike from Amad had fallen kindly for him inside the penalty box.
Mason Mount passed up an excellent chance to make it 2-1 in the period that followed after more good work from Amad, with Plzen's goalkeeper on hand to deny the Englishman.
Man United did have a second in the 88th minute, though, when Hojlund collected a free kick from Fernandes before firing into the back of the net to secure a huge three points for the 20-time English champions.
Man United's final two matches in the league phase of the competition will come against Rangers and FCSB in January, while Plzen will take on Anderlecht and Athletic Bilbao in their last two games next month.
VIKTORIA PLZEN VS. MAN UNITED HIGHLIGHTS
Matej Vydra goal vs. Man United (48th min, Viktoria Plzen 1-0 Man United)
Horrible mistake from Onana, as the Man United goalkeeper passes it straight to Sulc, who squares for Vydra, and the forward cannot miss; Onana was warned in the first period, and the hosts have now made the breakthrough; the pass into De Ligt was never on.
Rasmus Hojlund goal vs. Man United (62nd min, Viktoria Plzen 1-1 Man United)
Man United level the scores here, as Hojlund converts from close range after excellent work from Amad, who had worked worked his way into the Plzen box before shooting, and it broke for Hojlund, who makes it 1-1.
Rasmus Hojlund goal vs. Man United (88th min, Viktoria Plzen 1-2 Man United)
Incredible goal! Man United score their second of the match, and Hojlund has his second, with the Denmark international collecting a free kick from Fernandes before firing into the back of the net; the Red Devils have turned this around!
MAN OF THE MATCH - AMAD DIALLO
Amad was quiet in the first period, but he burst into life after the break, with the Ivory Coast international proving to once again be Man United's biggest threat due to his close control and running ability.
The attacker played a vital role in Man United levelling the scores, and he could have finished the night with a couple of assists had his teammates had their shooting boots on, with Amad demonstrating his class.
The 22-year-old also finished the night with a pass success rate of 93%, completing 41 of his 44 passes.
VIKTORIA PLZEN VS. MAN UNITED MATCH STATS
Possession: Viktoria Plzen 32%-68% Man United
Shots: Viktoria Plzen 15-17 Man United
Shots on target: Viktoria Plzen 2-8 Man United
Corners: Viktoria Plzen 1-5 Man United
Fouls: Viktoria Plzen 11-11 Man United
BEST STAT
WHAT NEXT?
Man United's attention will now switch back to the Premier League, with the Red Devils having the small matter of a trip to the Etihad Stadium on Sunday afternoon to tackle a wounded Manchester City; Amorim's side are currently 13th in the Premier League table, eight points behind Pep Guardiola's side in fourth.
Plzen, meanwhile, will continue their domestic season at home to Ceske Budejovice on Sunday evening; Miroslav Koubek's side are currently second in the Czech First League, 10 points behind runaway leaders Slavia Prague.
Written by
Matt Law