Carlisle were left to rue another Matty Glennon mistake which cost his side a share of the points at the Abbey Stadium.
Ironically the error was superseded by a string of fine saves - but the damage was already done.
A philosophical Carlisle boss, Roddy Collins, said after the game: "In the last two games we have been ahead but could not hold onto the lead.
"At one-all, I wasn't too concerned even though they have a lot of pace and Omer Riza up front can cause problems.
"I always felt they were vulnerable on the break and I thought if we could stop the flow of ball from their midfield our counter-attacking football would give us a return from the game.
"The winning goal was a sickener, but football is the cruellest game in the world.
"On another day Matty Glennon would have made the save and Craig Farrell's goal would have been allowed, but that's football."
Cambridge started well, Shane Tudor making a surging run from midfield before laying the ball into the path of Luke Guttridge who shot narrowly wide.
Tudor was again provider moments layer, finding Dave Kitson, whose flick on was headed wide by Guttridge.
On 11 minutes, Carlisle almost took the lead when Mark Magennis' delicate through ball found John Sutton, but Shaun Marshall got down well to turn his shot away.
Sutton only had nine minutes to wait to make amends by opening the scoring. Mark Summerbell found Leon Osman, who turned neatly to play in Sutton and the on-loan Tottenham striker calmly tucked his chance away.
The lead was short lived as Cambridge drew level five minutes later. Tony Scully's pass was missed by McGill and Tudor took advantage of the space to rifle a shot into the bottom corner from 30 yards.
Glennon then made brilliant saves from Riza twice while Osman shot narrowly wide the Cumbrians.
Four minutes into the second half, Cambridge were unlucky not to take the lead when a thunderous 25-yard shot from Guttridge smashed against the bar after Tudor had squared the ball into his path.
The increasingly busy Glennon had to be alert to save well from Tudor but the Carlisle keeper turned villain on 64 minutes.
Tudor picked up a loose ball on the edge of the box and his shot squirmed out of Glennon's hands but the keeper was unable to recover in time to avoid the ball crossing the line.
Glennon continued to be kept busy brilliantly turning over a Nacca effort and turning away a shot from Jordan.
The Cumbrians were then unlucky not to draw level as Farrell timed his run to perfection to slot home, only for the referee's assistant to make a mistake in flagging for offside.
Farrell again went close twice in the dying minutes but Cambridge keeper Marshall made impressive point blank saves.
Glennon then made the best save of the night, brilliantly tipping over a Tudor free kick in the last minute.
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