Skipper Phil Caddis, who scored the vital goal in the final game at Bolton last season to keep Birmingham in the Sky Bet Championship, again came to Birmingham's rescue with his 95th minute strike. Newcomer Mark Duffy added a third ten minutes later.
But Birmingham made hard work of their belated success after they had achieved an early break-through with the opening goal from Clayton Donaldson in the 16th minute.
Birmingham, however, were indebted a minute earlier to their Irish goalkeeper, Colin Doyle, who was making one of his rare appearances.
Twice in quick succession he saved from Kwesi Appiah and Adam Cunningham but in Birmingham's next attack Caddis slipped a pass into the path of the unmarked Donaldson who coolly picked his spot to score with a low shot to the left of goalkeeper Chris Dunn.
Cambridge, the League newcomers, competed well and it was Ryan Donaldson who put the U's back on level terms in the 37th minute with a fast solo run which he finished off in style with a low powerful shot from 20 yards.
The U's were boosted by this goal and a ragged Birmingham began to struggle. They were only kept in the game by Doyle's heroics highlighted with his one-on-one save to prevent Delano Sam-Yorke putting Cambridge ahead.
Cambridge took the game into extra time but were fortunate to survive as Clayton Donaldson's 89th minute effort off the back of his head hit the post from only a couple of yards.
But five minutes into extra time Caddis was on hand to crash a low shot through a packed defence and Duffy then added a third in the 105th minute.