Hojlund replaced Marcus Rashford in the 56th and scored an equalizer six minutes later after Amad Diallo's shot was deflected by goalkeeper Martin Jedlička into his path for an easy finish.
The 21-year-old Hojlund also scored twice in the previous round, when United beat Norwegian team Bodø/Glimt 3-2, and has five goals in his six appearances in the second-tier competition.
“It feels good to have scored two goals but I am more happy with the win,” Hojlund said. "My instructions? Go out there and score two goals! Just to use my qualities, run the channels and be assertive in front of goal.”
United had come off two straight losses in the English Premier League, 2-0 away to Arsenal, and 3-2 at Old Trafford to Nottingham Forest that left the club 13th and eight points adrift of the top four as progress looked slow under new coach Ruben Amorim.
Matěj Vydra, who previously played for Burnley and Watford, opened the scoring three minutes into the second half.
United has 12 points from six games after three wins and three draws in Europa League play — good enough for seventh place.
The top eight qualify directly to the Round of 16. The teams placed No. 9 to No. 24 go into a two-legged playoff.
Tottenham continued to show inconsistent form in a 1-1 draw at Rangers, leaving the north London team in ninth place. The Scottish side is eighth.
Substitute Dejan Kulusevski was fed by fellow substitute Dominic Solanke to score 15 minutes before time and salvage a point at Ibrox Stadium.
Spurs were held 2-2 at home by Roma in the previous round and lost 3-2 to Galatasaray before. The draw came after losing 4-3 to Chelsea in the Premier League on Sunday.
Hamza Igamane netted for Rangers at the start of the second half off a cross from James Tavernier in what was a return to Glasgow for Spurs coach Ange Postecoglou, who led Celtic for two seasons.
Fisayo Dele-Bashiru and veteran Pedro Rodríguez scored one each for Lazio in the second half to defeat Ajax 3-1 in Amsterdam and move to the top of the standings with 16 points from six games. Bilbao is level on points but in second on goal difference.
Anderlecht beat Slavia 2-1 in Prague to move into third place.
Lyon jumped to fourth by beating Eintracht Frankfurt 3-2. The German team is fifth.
Among other results, substitute Sergio Peña equalized in stoppage time for Malmö to hold unbeaten Galatasaray 2-2. The Turkish club is sixth in the standings. PAOK routed Ferencvaros 5-0.
Roma showed signs of improvement by beating Braga 3-0 for a second straight victory that came after the struggling club earned its first win under new coach Claudio Ranieri, 4-1 over visiting Lecce in Serie A.
Braga goalkeeper Matheus received a red card in the 68th with the score 2-0.
Rangers host Tottenham later Thursday.
Conference League
A youthful Chelsea lineup made the most of a long trip to Kazakhstan by beating Astana 3-1 to stay perfect in the UEFA Conference League.
Marc Guiu struck twice within five minutes early in the first half. The 18-year-old forward opened the scoring on a solo effort in the 14th and added his second after meeting a cross from Pedro Neto from the right in freezing conditions in the city of Almaty.
Guiu, who joined Chelsea from Barcelona this summer, has scored three in the competition.
Renato Veiga, who is 21, headed home the third before Marin Tomasov scored for the hosts late in the first half.
Neto was the only player to remain from the squad that beat Tottenham 4-3 on Sunday to move to second in the Premier League.
Chelsea has 15 points atop the standings of third-tier competition with one more game to play in the league phase.
Fiorentina crushed LASK 7-0 and Legia Warsaw lost 2-1 at home to Lugano. Swedish team Djurgarden beat Vikingur 2-1 in Iceland.
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