United had battered away at Boro's dogged defence without success until Berbatov relieved the tension for the English, European and newly crowned World Champions.
Cristiano Ronaldo found Ji-Sung Park in the centre of the Boro box. He flicked the ball left to Michael Carrick and, although his initial cross was blocked, the England midfielder knocked the rebound back into the centre.
Boro defender David Wheater failed to clear the danger with a downward header which landed perfectly for Berbatov to lash the ball right-footed into the net from eight yards.
It was a frustrating night for United and Ronaldo in particular.
Barged over in the box by Emanuel Pogatetz in the closing seconds of the first half, Ronaldo continued his argument with the Boro player as they left the pitch at the interval.
Ronaldo also went close on a number of occasions with shots from all distances and all angles.
His best chance was a glaring 22nd minute miss when he fired wide from ten yards at the near post after Wayne Rooney had picked him out with a pin-point cross from the left.
But Ronaldo was not the only United player to feel the frustration.
Rooney must also have wondered what he had to do to score, although in his case it was largely due to the brilliance of Boro goalkeeper Ross Turnbull.
With the first half moving into injury time, Darren Fletcher fired a long ball out of defence. Ronaldo headed the ball on to Rooney coming up on the left and he hit a vicious shot, which Turnbull superbly turned away at full stretch.
Turnbull had also denied Rooney early on when he palmed away another good effort from the England striker.
Turnbull did well to save further shots from Ronaldo and Park, while at the other end, United goalkeeper Edwin van der Sar was rarely troubled.
United's win now puts them seven points behind leaders Liverpool with two home games in hand- a position with which Ferguson and his men will be happy with as they enter the New Year.