Ronaldo popped up in the last of five minutes of stoppage time to score and give United a 2-1 win over Villarreal at Old Trafford
Barcelona plunged even further into crisis Wednesday with a thumping Champions League defeat at Benfica while holders Chelsea were beaten by Juventus but Cristiano Ronaldo grabbed a precious last-gasp winner for Manchester United.
Ronald Koeman's Barca side already look at real risk of an early exit from this season's Champions League after suffering a second 3-0 defeat in as many games in Group E and finishing the match in Lisbon with 10 men.
Uruguayan forward Darwin Nunez starred for Benfica, opening the scoring early on and then hitting the post early in the second half. He later completed the rout from the penalty spot following a Sergino Dest handball, while in between Rafa Silva also netted for the Portuguese former European Cup winners.
Eric Garcia was sent off for Barca, who have now conceded 11 goals in their last two visits to the Estadio da Luz, the scene of their 8-2 annihilation at the hands of Bayern Munich in the 2020 quarter-finals.
Barca are rock bottom of their group while Bayern followed their victory at the Camp Nou a fortnight ago with a 5-0 home win over Dynamo Kiev, with Robert Lewandowski's first-half brace setting the Bavarians on their way.
Lewandowski, who netted the opener from the penalty spot, now has a career tally of 77 Champions League goals, third in the all-time list behind Ronaldo and Lionel Messi.
Serge Gnabry, Leroy Sane and Eric Maxim Choupo-Moting added further goals after the break for a rampant Bayern.
Barca's defeat leaves Koeman - who took Benfica to the Champions League quarter-finals in 2006 - in an even more fragile position.
They have made it to the knockout rounds in each of the last 17 seasons.
Chelsea will still be expected to qualify for the last 16 despite losing 1-0 to Juve in Turin with Federico Chiesa scoring the only goal of the game 10 seconds into the second half.
The star of Italy's Euro 2020-winning side latched onto Federico Bernardeschi's assist to beat Edouard Mendy and give Massimiliano Allegri's team a second straight win in Group H.
Juve are still adapting to life since the return of Allegri as coach and the departure of Ronaldo but this could be a formative result for them against the holders.
Chelsea had started their defence of the trophy with a 1-0 win over Zenit Saint Petersburg, and the Russian champions bounced back to beat Malmo 4-0.
Claudinho, who won Olympic gold with Brazil in Tokyo, opened the scoring before Daler Kuzyaev, Aleksei Sutormin and Wendel all added second-half goals.
Ronaldo popped up in the last of five minutes of stoppage time to score and give United a 2-1 win over Villarreal at Old Trafford.
Jesse Lingard cutely set up Ronaldo to score his record-extending 136th goal in the competition as United bounced back from their last-gasp defeat to Young Boys in Bern last time out.
Alex Telles had earlier hauled the hosts back level on the hour mark with a superb first-time volley from a Bruno Fernandes delivery for his first goal for Ole Gunnar Solskjaer's side.
Paco Alcacer had given Villarreal the lead in what was a rematch of last season's Europa League final, won by the Spanish outfit on penalties.
United and Young Boys trail a point behind Group F leaders Atalanta, who defeated the Swiss champions 1-0 in Italy with a Matteo Pessina goal.
Teenage German starlet Karim Adeyemi netted two penalties, one in each half, as Red Bull Salzburg beat French champions Lille 2-1 to go top of Group G on four points.
Burak Yilmaz pulled one back for Lille but they prop up the section, while Sevilla snatched a 1-1 draw at Wolfsburg after a late Ivan Rakitic penalty cancelled out Renato Steffen's opener for the Germans, who had Josuha Guilavogui sent off.
Benfica 3 (Nunez 3, 79-P, Silva 69) Barcelona 0
Bayern 5 (Lewandowski 12-P, 27, Gnabry 68, Sane 74, Choupo-Moting 87) Kyiv 0
Atalanta 1 (Pessina 68) Young Boys 0
Man Utd 2 (Telles 60, Ronaldo 90+5) Villarreal 1 (Alcacer 53)
Salzburg 2 (Adeyemi 35-P, 53-P) Lille 1 (Yilmaz 62)
Wolfsburg 1 (Steffen 48) Sevilla 1 (Rakitic 87-P)
Zenit 4 (Claudinho 9, Kuzyaev 49, Sutormin 80, Wendel 90+4) Malmo 0
Juventus 1 (Chiesa 46) Chelsea 0