Adam Tann popped up to grab a dramatic late winner as injury-hit Cambridge left rivals Northampton with maximum points.
But Northampton, who played for most of the game with only ten men after Chris Willmott's first-half dismissal, produced a performance that deserved a point after a battling second-half display.
Cambridge made a lively start with Danny Webb being denied early on by Cobblers keeper Lee Harper, while at the other end Richard Walker tested Shaun Marshall and Martin Smith flashed a volley just wide.
The game turned in the 27th minute when Webb, making his debut after being signed on-loan from Hull City, was brought down by Willmott in the box.
Willmott was shown the red card and Luke Guttridge made no mistake from the ensuing penalty.
Marc Richards should have equalised with a far-post header while Cambridge substitute David Bridges went close with a near-post diving header.
Guttridge had a great opportunity to double his side's advantage when Paul Reid sent Francesco Nacca sprawling in the box in the 51st minute, but, after a lengthy delay, he saw Harper brilliantly turn away his spot-kick.
Northampton deservedly drew level in the 72nd minute when substitute Derek Asamoah raced clear and beat Marshall with a low drive from the edge of the box.
Three minutes later Northampton had a great opportunity to take the lead when Asamoah pulled the ball back for Paul Harsley, whose goal-bound shot struck his team-mate Smith and rebounded clear.
However, Cambridge were not to be denied and with two minutes of normal time remaining a neat build-up ended with Tann grabbing the winner from close range.