Michael Carrick remained his trademark composed self while watching on from the touchline
Much of the second-half also passed by without little to note, De Gea again making crucial stops while Jadon Sancho spurned United's best chance of the night shortly after.
However, Cristiano Ronaldo would go on to be the match winner with a perfectly weighted lob in the 78th minute to continue his dominant display on the continent this season.
Sancho secured his first goal for the club late on with a fierce right-footed effort that thundered in off the underside of the cross-bar to secure the victory.
The result means United can tackle their next group stage game at home to BSC Young Boys without fear of elimination from Europe's most elite competition.
Read more : 5 changes Michael Carrick made for Villarreal vs Man Utd including new Ronaldo role
Ronaldo’s Champions League heroics continue
Cristiano Ronaldo scored the crucial goal during Man Utd's win over Villarreal
A late strike for Cristiano Ronaldo secured United’s progression to the knockout stages of the Champions League and also marked the 799th goal of his career.
Carrick’s tactics slowly became more progressive as the game wore on, United defending from the front valiantly – Villarreal's harried defence buckling under pressure to present Ronaldo with the chance to notch his sixth goal in five European games this term.
As he has been so many times already this term, the 36-year-old was United’s most potent attacking threat for the whole game before eventually making his opponents pay.
A delicate lob stunned the Estadio de la Cerámica into silence, while also sending United into the knock-out stages of the competition.
Bruno Fernandes the first Carrick casualty
Bruno Fernandes spent the first hour of Man Utd's contest with Villarreal on the bench
The Portugal international has been nothing short of a revelation since he made the move to Manchester nearly two years ago, but was taken out of the firing line tonight after his heated exchange with fans at the weekend.
Having witnessed Fernandes remonstrated with the United away faithful following the humiliating 4-1 defeat at Watford on Saturday, Carrick made his first statement decision by dropping the midfielder from the starting line-up.
Coy in his pre-match remarks, United’s interim boss was pressed on his decision, but simply said: “Not one of the players have been at their best.
“I love Bruno, I think he’s a fantastic player and a great person but he has played a lot of games and ran his socks off on Saturday.”
Fernandes was eventually introduced in the 65th minute, immediately increasing the quality of United's performance.
McFred remain the favoured choice
Scott McTominay struggled defensively against Unai Emery's side
One of the most maligned midfield duos in Man Utd’s recent history, both Scott McTominay and Fred found it particularly difficult to gain any kind of foothold on the contest.
Given their recent dismal displays under Solskjaer, many may have expected at least one of them to drop out of the starting line-up in place of a more seasoned veteran such as Nemanja Matic.
The first-half possession stats made for grim reading for United’s midfield pairing, Villarreal comfortably enjoying the lion's share of the ball for much of the first period.
Not only was there a lack of control in proceedings, there was an evident lack of progression from both players throughout.
The pair's seeming inability to block off passing avenues ensured the likes of Etienne Capoue and Dani Parejo were allowed to break lines and spark attacks on multiple occasions.
Donny van de Beek starts
Donny van de Beek was handed the chance to impress from the off against Villarreal
One of the most bizarre additions in Man Utd’s recent history, the undeniably talented former Ajax prodigy was purchased for £40m to then spend nearly a season and a half almost entirely on the bench under Solskjaer.
However, his inclusion in tonight’s starting eleven could mark a shift in the Dutchman’s fortunes at the club.
Fresh off of his consolation goal on Saturday evening, rather poetically the last of the Solskjaer-era, Donny van de Beek was handed a start under interim boss Carrick and for the most part left a lot to be desired.
A passenger for much of the first-half, Van de Beek’s strongest assets were nullified given Villarreal were the more dominant of the two sides, ensuring United attacks were few and far between.
The 24-year-old even picked up a yellow card for his troubles following a late challenge, ensuring he spent from minute 40 onwards on a tightrope before he was eventually hauled off just after the hour mark.
Referee Felix Brych was forced to delay kick-off due his original communication system failing
The pre-match nerves were worn on the faces of a number of United stars as they lined up, the Champions League anthem ringing in their ears only likely to heighten the tension – before something out of the ordinary led to even more anxiety.
A communication issue between the match-officials led to a further delay, again adding another layer to the dynamic of United’s nerves.
A number of footballs were sprayed on to the pitch to allow the players to get a feel for the ball before kick-off, but as referee Felix Brych desperately searched for a microphone pack that had working batteries – United’s stars were left with their own thoughts.
The fact a Champions League contest in this day and age was delayed for seven minutes due to a lack of batteries in itself is somewhat remarkable, but it is likely to have only hindered a number of the players from both sides and their pre-match preparations.