Keigan Parker's solitary strike was enough for Mansfield to overcome the 10 men of Cambridge.
The home side dominated throughout and went close through striker Louis Briscoe and midfielder Tyrone Thompson in the first half.
Cambridge were reduced to 10 men when defender James Jennings received a straight red card for a deliberate hand ball on the goal line.
Parker then scored his first goal for the club from the resulting penalty.
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Mansfield:
Marriott, Sandwith, Foster, Chris Smith, Silk, Adam Smith (Duffy 84), Thompson, Mills, Briscoe (Nix 64), Connor, Parker (Medley 73). Subs Not Used: Collett, Naylor.
Goals: Parker 62 pen.
Cambridge Utd:
Brown, Jennings, Saah, Coulson, Roberts (Ives 11), Platt (Coakley 63), Carden, Miller, Russell, Willmott (Clare 70), Wright. Subs Not Used: Naisbitt, Gray.
Sent Off: Jennings (61).
Att: 2,257.
Ref: Darren Bond (Lancashire).
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