David Bridges scored the only goal of the game to give Cambridge an impressive victory at Christie Park.
Bridges struck home a crisp 20-yard effort which proved enough to secure the points despite the best efforts of Morecambe, who had several chances.
Wayne Curtis went close for the Shrimps - forcing a good save from Scott Howie - and he and Michael Twiss also missed from close range as time ticked down.
Cambridge had Danny Bunce sent off late on for a second bookable offence.
Morecambe: Robinson, Hardiker, Bentley, Kempson, Howard (O'Connor 74), Thompson, Perkins, Brannan, Curtis, Carlton, Twiss. Subs Not Used: Kelly, Lloyd, Walmsley, Davies.
Booked: Twiss, Bentley.
Cambridge Utd: Howie, Morrison, Duncan, Peters, Bridges, Quinton, Smith, Nicholls, Bunce, Atkins (Westcarr 83), Nolan (Hanlon 90). Subs Not Used: Behcet, Robbins, Okai.
Sent Off: Bunce (90).
Booked: Duncan, Bridges, Bunce, Peters, Nolan.
Goals: Bridges 17.
Ref: R Lewis (Shropshire).