Cambridge promoted to League Two
United had twice lost play-off finals following their relegation from the Football League in the 2004-05 season.
However, the club can now celebrate a return to League Two after prevailing in a tense encounter at Wembley.
Richard Money's Cambridge finished second in the Conference behind champions Luton and overcame FC Halifax Town in the play-off semi-finals, while third-placed Gateshead saw off Grimsby Town.
A cagey first half of the final ended goalless, but Cambridge took control after the interval.
Liam Hughes nodded in a right-wing cross from former Gateshead man Ryan Donaldson to put Money's men ahead in the 51st minute.
A delightful free-kick from Donaldson doubled Cambridge's lead 20 minutes later.
However, a nervy finish followed after Jack Lester pulled a goal back for Gateshead, with the north-east club spurning a number of late chances to draw level.
Cambridge also had to cope with 10 men in the closing stages after Ian Miller was forced off through injury with his side having made all three substitutions, but Gateshead could not capitalise.