Tom Naylor's own goal was enough to give Cambridge a 1-0 victory at faltering Grimsby.
The hosts came into the game following back-to-back defeats, but went close to opening the scoring when Shaun Pearson glanced Jamie Devitt's 18th-minute corner inches wide of the far post.
It was at the other end where the breakthrough was made when Naylor headed Harrison Dunk's curling free-kick into his own net to give the U's the advantage after 27 minutes.
Marcus Marshall almost levelled the scores five minutes later but his right-footed strike from the edge of the area flashed wide.
Naylor had the chance to make amends for his error in the 57th minute when he raced through on goal, but chipped wide of the post with Nick Pope stranded.
Dunk tested James McKeown in the closing stages as Richard Money's side held on to their precious lead with relative ease to earn their first victory against the Mariners in 20 years.