The prolific Bulgarian now has 18 goals this season and yet another match ball to go alongside those he collected against Liverpool and Blackburn earlier in the campaign.
More importantly for Sir Alex Ferguson, his side tightened their grip on top spot, with Ryan Giggs and Nani also finding the net as the leaders extended their unbeaten run this season to 22 games ahead of Tuesday's trip to Blackpool, the first of their matches in hand.
Berbatov for one will be looking forward to his first outing at Bloomfield Road, knowing just how much damage he is capable of inflicting.
It has been said so often United are way below their best this season that it is almost accepted truth.
Yet a three-goal first-half salvo gave lie to the theory as the visitors were pummelled from every angle.
There were less than two minutes on the clock when Ryan Giggs chipped a corner to the near post.
John O'Shea, making his first appearance since the end of November, stooped to flick on and Berbatov, two yards out, could not miss.
Berbatov was denied a second virtually straight away as he strode onto Rooney's pass and fired a fierce shot at the Birmingham goal that former Red Devil Ben Foster kept out with his feet.
It may not be quite the swashbuckling manner of Cristiano Ronaldo, or Eric Cantona before him, but United now appear to strangle the life out of opponents, tightening their grip mercilessly once an advantage has been established.
The method is not foolproof, as Birmingham proved with their late equaliser at St Andrew's three weeks ago.
But United are pretty good at exerting their power and once Birmingham had not profited from an enterprising flurry of attacks, it was no surprise when they scored again.
If this is a season to forget, goalscoring wise, for Rooney, Berbatov is having the time of his life.
Driving through the heart of Birmingham's defence, the England star rolled a precise pass to his left, offering Berbatov the space to step inside Roger Johnson and beat Foster low at his near post.
Berbatov was close to completing his latest hat-trick on United's next attack.
He did not know it at the time, but as he watched his curling effort fly inches wide of Foster's goal, the wait was not going to be too long.
United did score again before the break, a move that proved Berbatov can do little wrong at present.
The former Tottenham star actually slipped as he tried to retrieve possession just outside the Birmingham box.
Yet somehow he still managed to rob Alexander Hleb despite being in the prone position. A couple of passes to Rooney later and his strike partner was crossing for Giggs, who rammed home at the far post.
Goal difference may yet become a factor later in the season and United had started the day better off in that regard than Mancunian rivals City. Berbatov, though, remained keen to help the cause yet further.
Yet another industrious piece of work from Rooney set his side in forward motion again.
Giggs was aware enough to know where Berbatov was and, once found in a central position barely six yards out, the rest was academic.
Not even Ronaldo claimed three hat-tricks in one season for all his scoring feats. And to think, there were plenty who felt Ferguson would jettison his club record signing last summer.
United kept going and Nani's repeated attempts to find the net finally paid off 13 minutes from time, when he cut in from the right and beat Foster from 20 yards.
More chances came and went. Rooney must wonder exactly what he has to do to get goals these days, whilst Nani and substitute Michael Owen also came close to a sixth.
It did not come. But after such an amazing season for his own team, Blackpool boss Ian Holloway's smile might turn into a frown when he considers how to stop Berbatov at Bloomfield Road on Tuesday.
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