Two goals in two second half minutes helped Morecambe come from behind to take three points at the Abbey Stadium.
A penalty from Jack Dunn and a fine goal from Paul Mullin saw the Shrimps take victory after Piero Mingoia had given the home side a first-half lead.
Cambridge went ahead in the 36th minute through former Accrington Stanley wide man Mingoia.
The home side broke quickly with Ben Williamson wasting a glorious chance to score when he took too long to get his shot off but the ball rebounded perfectly for Mingoia to drill a low shot past Barry Roche from just inside the edge of the area.
The goal came moments after the Shrimps had enjoyed their best spell of the game when Leon Legge deflected a Mullin cross inches wide of his own goal and the same Morecambe player had tested Will Norris with a close-range header.
After a sluggish first half the Shrimps were much brighter after the break with Dunn fizzing an early shot over the bar before winning a penalty after being bundled over by Luke Berry in the box.
After a bit of debate with Mullin it was Dunn who stepped up to take the kick and sent Norris the wrong way from the spot.
Two minutes later the Shrimps went ahead with Dunn found Mullin and he rounded Norris before slotting the ball into the net from an acute angle.
Cambridge had created the early chances and would have gone ahead on six minutes had Ben Williamson not blocked a shot from his own player Adam McGurk that looked destined for the Morecambe net.
On 18 minutes Medy Elito also had a good chance when the ball came to him on the edge of the area but he could only curl his effort wide of the left-hand post when he should have done better.
Elito was also guilty of missing a good chance when he shot wide from a good opening in the final stages of the game but the Shrimps defended well and bounced back from their 5-1 defeat against Doncaster in style.
Cambridge: Norris, Halliday, Coulson, Legge, Dunk, Mingoia, Newton (rep Clark 65), Berry, Elito (rep Taylor 81), Williamson (rep Ikpeazu 67), McGurk. Subs not used: Gregory, Dallison, Gosling, Pigott.
Morecambe: Roche, Wakefield, Winnard, Edwards, Conlon, Rose, Fleming (rep Murphy 77), Mullin (rep McGowan 85), Dunn, Ellison, Stockton (rep Massanka 80). Subs not used: Nizic, Kenyon, Molyneux, Jennings.
Referee: Darren England.