Cristiano Ronaldo made his comeback after ankle surgery and almost set up Jonny Evans for a late winner, only for the youngster to head against the post.
Guille Franco sent a flick against an upright on the hour as Villarreal provided stubborn resistance.
But the main plus for United boss Sir Alex Ferguson was a vibrant 25-minute cameo from the returning Ronaldo.
He now looks like he has put himself in the frame for a place in United's starting line-up for Sunday's clash with Premier League leaders Chelsea at Stamford Bridge.
Ronaldo, as expected, started on the bench - but Ferguson sprung a surprise by naming Evans in his starting line-up in place of Nemanja Vidic, who is suspended for the meeting with Chelsea.
United dominated the first half without ever hitting top gear against an efficient Villarreal side.
Rio Ferdinand wasted an opportunity to put United ahead after only seven minutes, but he was surprised when Owen Hargreaves' corner arrived at his feet and he miscued his effort off target.
Villarreal keeper Diego Lopez looked uncertain, and he was called into action to save efforts from Nani and Carlos Tevez.
United were denied what was a clear penalty eight minutes before the interval when Ji-Sung Park tumbled under Joan Capdevila's challenge, but German referee Wolfgang Stark waved away the appeals.
Villarreal fashioned the best move of the match and almost took the lead after 59 minutes when Franco flicked Angel Lopez's cross against the post with United keeper Edwin van der Sar beaten.
The moment Old Trafford had been waiting for arrived after 65 minutes when Ferguson unleashed Ronaldo - and the effect was instant.
Ronaldo received a rapturous reception, despite a summer of speculation linking him with a move to Real Madrid, and he was quickly a threat with a volley that worried keeper Lopez.
He then combined brilliantly with Rooney to set up Tevez after 71 minutes, but Gonzalo Rodriguez cleared off the line.
Ronaldo's presence had unnerved Villarreal, and he headed just wide from Nani's cross and then set up Evans with a perfect cross, only for the youngster to send a diving header against the post.
United pressed until the end, but Villarreal held on to frustrate the holders.
Manchester United manager Sir Alex Ferguson
"Cristiano Ronaldo has had a turbulent summer and a lot has been said about it, but when I had my meeting in June in Portugal with him that was over.
"He dedicated himself to getting fit and his commitment to the club. The crowd's reception was important for Cristiano.
"I think he realises what a great club he is at and how loyal the fans are. He will take great encouragement from that.
"We made a lot of good chances, we played really good football, we played with speed. I have no complaints. On another day we could have scored four or five.
"They are a very experienced side, very competitive team. They defend determinedly."
Man Utd: Van der Sar, Neville, Ferdinand, Evans, Evra, Nani, Hargreaves (Anderson 62), Fletcher, Park (Ronaldo 62), Rooney, Tevez (Giggs 81).
Subs Not Used: Foster, Brown, Vidic, O'Shea.
Booked: Tevez.
Villarreal: Diego Lopez, Angel, Rodriguez, Godin, Capdevila, Cani (Santi Cazorla 46), Eguren, Edmilson, Pires (Ibagaza 67), Fernandez, Franco (Llorente 77).
Subs Not Used: Viera, Javi Venta, Senna, Fuentes.
Booked: Franco, Ibagaza, Diego Lopez.
Att: 74,944
Ref: Wolfgang Stark (Germany).
BBC Sport Player Rater man of the match: Manchester United's Ji-Sung 7.11 (on 90 minutes).
