Fresher and more incisive throughout, Zenit took the lead when Pogrebnyak forced home a header from close range.
Playmaker Danny made it 2-0 with a fine solo goal on the hour, before Nemanja Vidic pulled one back from six yards.
It was too little too late, though, with Paul Scholes sent off late on in a lacklustre showing from United.
The midfielder saw red when he punched the ball into the net with only seconds left on the clock, earning himself a second booking and one-match European suspension that could see him sit out the Champions League group match against Villarreal.
It was a sorry end to the match for United, who had looked off the pace throughout.
With Zenit midway through the Russian season, the difference in sharpness between the sides was clearly evident, and Dick Advocaat’s side showed they could well be a threat in this season’s Champions League – even without Andrei Arshavin, who has been heavily linked with Spurs and who only played 45 minutes in Monaco.
The defeat, though, will not be too hard to take for United, who not only had Cristiano Ronaldo watching from the stands, but who will also be hoping to add a striker – most notably Dimitar Berbatov – to their ranks before the close of the transfer window on Monday.
United’s strikers, however, are yet to find the net after three matches of the new season, with Darren Fletcher scoring their only goals in both of the opening two Premier League fixtures.
United boss Sir Alex Ferguson said before the match that the traditional showpiece between the Champions League winners and the Uefa Cup champions was a game to be enjoyed, but there was little for the Scot to savour from the first 45 minutes.
Zenit impressed with an attractive counter-attacking style en route to Uefa Cup glory last season and the same style had United on the back foot throughout, particularly down the Russian side’s right, where Patrice Evra had a torrid time in the opening half.
Konstantin Zyryanov and Aleksandr Anyukov were a constant threat and they forged the first clear openings of the match when twice they combined to get behind the United defence, only for Pogrebnyak to spoon over when well positioned on both occasions.
Rio Ferdinand then had to be alert to deflect a Danny cross narrowly past the post, while at the other end a weak Carlos Tevez shot on 19 minutes was the best United could muster.
Ferguson’s side finally showed something like their best attacking play when Tevez forced an opening down the right wing, but Wayne Rooney dallied too long on his shot and the chance came and went.
And minutes after Ivica Krizanac had forced Edwin van der Sar into an instinctive save from close range, Zenit’s pressure finally told when Pogrebnyak forced the ball over the line after Igor Denisov had flicked on Dominguez’s corner seconds before half-time.
As if United were not struggling already, Arshavin was introduced at the break and his trickery immediately had the English champions on the back foot.
However, it was the diminutive Russian’s potential replacement – Danny – who lit up the second half, the £25m signing from Dinamo Moscow dancing through the United defence and finishing with aplomb to make it 2-0 on the hour.
Tevez, a rare bright spark for United, continued to play the workhorse role up front, though, and moments after the Argentine’s industry had almost set Rooney free in the box, he drilled a fine effort over.
It sparked a spell of pressure from United that had long been overdue, and with United’s game finally clicking into gear, Zenit struggled to cope.
It was no surprise, therefore, when Vidic reduced the deficit from Tevez’s pull-back after good work in the box by Rooney – and it preceded a last 20 minutes that saw United pile forward and Zenit attempt to pick holes in the Reds’ defence on the break.
John O’Shea and Park Ji-Sung both had good opportunities blocked in the box, while Zenit keeper Vyacheslav Malafeev did well to deny Rooney with the minutes ticking down.
However, the best chance of the latter stages fell to Zenit’s Danny, the Portuguese star latching onto Arshavin’s pass only to fire over with just Van der Sar to beat.
And United’s misery was complete a minute before time when Scholes was dismissed for an unnecessary handball.
Manchester United manager Sir Alex Ferguson:
“I think we played our best football at 2-0, unfortunately. It was a warm night and so I think my players did OK under the circumstances.
“I thought Tevez was outstanding – probably the best player on the park – and I thought we had chances to do something in the game.
“But Zenit are a very good team and have exceptional movement. They’ll be a force in the Champions League playing like that.”