Tom Naylor's own goal handed Cambridge victory and condemned promotion-chasing Grimsby to a third successive defeat.
Shaun Pearson almost headed the Mariners ahead, glancing Jamie Devitt's corner narrowly wide.
But the breakthrough came at the other end, as Naylor headed Harrison Dunk's free-kick into his own net.
Naylor had Grimsby's best chance to equalise, but could only chip wide when through on goal to cap off a miserable afternoon for the 21-year-old defender.
The result leaves the Mariners fifth, three points ahead of sixth-placed Forest Green having played three games fewer, while Cambridge move to ninth.
VIEW FROM THE DRESSING ROOM
Grimsby joint manager Rob Scott told BBC Radio Humberside:
"It's been a bit of a nightmare week.
"To lose the goal the way we did... I didn't feel it was a free kick in the first place. I think the referee was a bit over-zealous and probably watching a bit too much Champions League in the last few weeks.
"Everybody thinks we will probably be pressing the panic buttons but we can't do anything about that week.
"We've lost three games and because it comes in the space of seven days it knocks confidence and belief and makes it look all the worse."
Full Time The referee blows for the end of the match.
Andy Cook fouled by Josh Coulson, the ref awards a free kick. Shot comes in from Jamie Devitt from the free kick, save by Nick Pope. Corner taken right-footed by Joe Colbeck from the right by-line, Liam Hearn takes a shot. Blocked by Josh Coulson. Corner from the left by-line taken by Joe Colbeck, Nick Pope makes a save.
Jamie Devitt produces a cross, save by Nick Pope.
Substitution Nathan Blissett replaces Tom Elliott.
Corner taken right-footed by Joe Colbeck from the right by-line to the near post, Liam Hughes manages to make a clearance.
Free kick awarded for a foul by Aswad Thomas on Harrison Dunk. Kevin Roberts takes the free kick.
Substitution Shaun Pearson leaves the field to be replaced by Dougie Wilson.
Liam Hearn has an effort at goal from the edge of the box that misses to the right of the target.
Effort from outside the penalty box by Frankie Artus goes wide right of the target.
Harrison Dunk takes the direct free kick.
Booking Frankie Artus goes into the book.
Unfair challenge on Harrison Dunk by Frankie Artus results in a free kick.
Joe Colbeck takes the outswinging corner, Josh Coulson manages to make a clearance.
Joe Colbeck delivers the ball, save by Nick Pope.
Sam Hatton sends in a cross, Tom Shaw makes a clearance.
Harrison Dunk takes a shot. James McKeown makes a save.
Sam Hatton sends in a cross, save made by Nick Pope.
Corner from the right by-line taken by Joe Colbeck, save by Nick Pope.
Shot by Tom Shaw from deep inside the penalty area misses to the right of the goal.
Shaun Pearson takes a shot. Josh Coulson gets a block in. Corner from left by-line taken by Joe Colbeck.
Foul by Rossi Jarvis on Liam Hearn, free kick awarded. Joe Colbeck delivers the ball from the free kick right-footed from left wing, clearance made by Kevin Roberts.
Substitution Liam Hearn replaces Richard Brodie.
Substitution (Grimsby) makes a substitution, with Joe Colbeck coming on for Marcus Marshall.
The ball is delivered by Tom Elliott.
A cross is delivered by Aswad Thomas, clearance by Josh Coulson.
Unfair challenge on Harrison Dunk by Frankie Artus results in a free kick. Free kick taken by Nick Pope.
Free kick awarded for an unfair challenge on Curtis Haynes-Brown by Marcus Marshall. Nick Pope restarts play with the free kick.
Tom Naylor produces a right-footed shot from long range which goes wide right of the goal.
Inswinging corner taken left-footed by Harrison Dunk, clearance made by Shaun Pearson.
A cross is delivered by Rossi Jarvis.
Tom Elliott challenges Shaun Pearson unfairly and gives away a free kick. Direct free kick taken by James McKeown.
Richard Brodie takes a shot. Save by Nick Pope.
Centre by Rossi Jarvis, save by James McKeown.
Shaun Pearson concedes a free kick for a foul on Tom Elliott. Harrison Dunk sends in a cross, Effort from inside the area by Tom Shaw misses to the right of the goal.
The second half begins.
45:00 +2:05 Half time
Half Time The referee calls an end to the first half.
Liam Hughes takes a shot. Save made by James McKeown.
Richard Brodie sends in a cross.
Shot from just outside the box by Richard Brodie goes over the crossbar.
Liam Hughes takes a shot. Blocked by Shaun Pearson.
Corner taken left-footed by Harrison Dunk from the right by-line, Josh Coulson takes a shot. Blocked by James McKeown.
Marcus Marshall sends in a cross.
Tom Naylor takes a shot. Tom Shaw gets a block in.
Richard Brodie produces a cross, clearance made by Josh Coulson.
Marcus Marshall concedes a free kick for a foul on Curtis Haynes-Brown. Direct free kick taken by Nick Pope.
Frankie Artus sends in a cross, Charlie Wassmer makes a clearance.
Inswinging corner taken left-footed by Harrison Dunk, Sam Hatton manages to make a clearance.
Centre by Aswad Thomas.
Marcus Marshall produces a right-footed shot from the edge of the area and misses to the left of the goal.
Richard Brodie fouled by Charlie Wassmer, the ref awards a free kick. Free kick crossed by Sam Hatton, save made by Nick Pope.
Andy Cook challenges Curtis Haynes-Brown unfairly and gives away a free kick. Free kick taken by Charlie Wassmer.
Assist by Harrison Dunk.
26:17 Goal scored
Goal! - Tom Naylor - Grimsby 0 - 1 Cambridge Headed own goal by Tom Naylor. Grimsby 0-1 Cambridge Utd.
Liam Hughes fouled by Frankie Artus, the ref awards a free kick. Harrison Dunk takes the direct free kick.
Centre by Curtis Haynes-Brown.
Jamie Devitt takes the outswinging corner, Headed effort from close range by Shaun Pearson goes wide left of the target.
The ball is crossed by Marcus Marshall, clearance made by Charlie Wassmer.
Inswinging corner taken right-footed by Tom Shaw from the left by-line to the near post, clearance made by Frankie Artus.
Shot from just outside the area by Jamie Devitt goes over the bar.
Richard Brodie handles the ball and concedes a free kick. Free kick taken by Nick Pope.
Foul by Charlie Wassmer on Andy Cook, free kick awarded. Direct free kick taken by Sam Hatton.
Sam Hatton delivers the ball, Nick Pope makes a save.
Liam Hughes produces a cross, clearance made by Sam Hatton.
Free kick awarded for an unfair challenge on Shaun Pearson by Tom Elliott. Direct free kick taken by James McKeown.
The ball is swung over by Harrison Dunk, Tom Elliott produces a header from inside the area that goes over the bar.
Jamie Devitt crosses the ball, clearance made by Nick Pope.
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