Ruben Amorim's United side came from behind to best the Czech side thanks to a second-half brace by Danish striker Hojlund, they now sit seventh in the league phase standings.
"The win is important at the moment and it's good to prepare for the next game," United manager Amorim told TNT Sports.
A top-eight finish will see United qualify automatically for the round of 16, while finishing ninth to 24th will earn them a play-off tie to reach that stage.
Matej Vydra opened the scoring three minutes after half-time to stun United, before substitute Hojlund scored twice in the last half-hour to seize a vital three points for the English club.
The winner came two minutes from time when Bruno Fernandes cleverly slipped a free-kick into the 21-year-old's feet and he held off a defender before slipping home.
Elsewhere in the Europa League, Spurs drew 1-1 with Rangers in Glasgow.
The hosts sit in the final automatic qualification spot with Spurs one place below them, but both level on 11 points.
"We took the challenge with both hands, grabbed it and showed what we wanted them to show," said Rangers manager Philippe Clement.
"We deserved to win the game, but I think it was a very good advertisement for Scottish football to compete with a Premier League team at full strength."
A draw somewhat eases the pressure on Spurs boss Ange Postecoglou, after his side went into the match with just one win in their last seven outings in all competitions.
Rangers took the lead two minutes after the interval when Moroccan striker Hamza Igamane continued his fine start to life in Glasgow by netting his fourth goal in as many European outings this season.
Captain James Tavernier bent an excellent inswinging pass from the right flank beyond the Spurs defence and into the path of Igamane who finished unerringly at the far post.
Substitutes Dominic Solanke and Dejan Kulusevski combined to bring the English side level with a quarter of an hour remaining, the Swede wrong-footing the goalkeeper with a cool finish from just inside the box.
Fraser Forster made a vital save from Cyriel Dessers to keep Spurs level in the last 10 minutes, and moments later the Rangers striker had a goal disallowed for offside.
"(It was) a great save by Fraser at the end. It's an important point," said Postecoglou.
Lazio top the standings with 16 points -- joint with Athletic Bilbao -- after beating Ajax 3-1 in Amsterdam to book their spot in the knock-out stages.
Lyon beat Eintracht Frankfurt 3-2 to move up to fourth -- one place above the in-form Bundesliga club.
Anderlecht overcame Slavia Prague 2-1 in the Czech capital to jump to third in the standings.
'Solid performance'
A much-changed Chelsea side beat Astana 3-1 in the Conference League to guarantee a top-eight finish in the league phase -- ensuring automatic qualification to the round of 16.
"It was a solid performance. We knew it was quite cold. We tried to adapt quickly. The players did fantastically with the weather conditions and the long journey yesterday," said Chelsea manager Enzo Maresca.
Chelsea sit top of the standings on 15 points after five matches, two ahead of Vitoria Guimaraes who won 4-1 at Swiss side St Gallen.
Chelsea wrapped up the points in the first half through goals from Marc Guiu and Renato Veiga.
Marin Tomasov pulled one back for the hosts on the stroke of half-time but Maresca's side rarely looked troubled in the second half as they closed out the win.
Spanish teenager Guiu gave Chelsea the perfect start by netting a brace inside the opening 20 minutes, bringing his tally in Europe to three goals in five appearances this season.
Last season's defeated finalists Fiorentina won 7-0 at home to Austria's LASK Linz as they ensured progression to the knockout stages.
