Town looked to have made the better start to the game and played some good football in the first half but lacked an end product in front of goal.
But after taking the lead, the hardworking Cambridge side were fully deserving of their win and could have increased their margin of victory but for missed chances in the second half.
Town kept searching for the goal that would have salvaged a point but ultimately, they could not find a breakthrough.
Grimsby bosses Rob Scott and Paul Hurst sprang a surprise by naming striker Liam Hearn on the bench after he had been out of action through injury since August.
Another surprise inclusion was Frankie Artus, who replaced injured skipper Craig Disley in midfield, while Richard Brodie came into the starting XI in attack in place of Ross Hannah, who also picked up an injury in the midweek defeat at Mansfield.
James McKeown started in goal, with Sam Hatton, Shaun Pearson, Ian Miller and Aswad Thomas forming the defence.
Jamie Devitt, Artus, Naylor and Marcus Marshall were the midfielders, with Andy Cook named alongside Brodie up front.
Hearn made a welcome return to the matchday squad as one of the substitutes and last season’s top goalscorer was joined on the bench by Joe Colbeck, Bradley Wood, Lennell John-Lewis and Dougie Wilson.
Town were looking to return to winning ways after suffering back-to-back losses for the first time this season in their previous two games against Mansfield and Kidderminster.
The Mariners were looking to keep their automatic promotion hopes going, while their visitors from Cambridge were looking to improve on their mid-table position in the Blue Square Bet Premier by collecting all three points.
The main threat from the away side was likely to come from 13-goal top scorer Tom Elliott, while Harrison Dunk and Andy Pugh would be out to cause problems for the Grimsby defence down the flanks.
Town began the game looking to keep possession, playing the ball to feet and patiently building up attacks.
The first chance of the game went to the visitors though, with Dunk getting down the right and crossing for Elliott to head over the bar from 12 yards.
More good football from the Mariners came on six minutes with a move that ended with a cross from Hatton on the right but it proved comfortable for visiting keeper Nick Pope to collect.
A foul by Charlie Wassmer on Cook gave Grimsby a free kick inside the Cambridge half on ten minutes but again, Hatton’s delivery was caught by Pope.
Devitt picked the ball up on the left four minutes and set off on a run, cutting in and firing a shot over the bar from 25 yards.
A Cambridge corner soon afterwards was headed away by Artus, before Brodie did well to win Town’s first corner of the game at the other end. Devitt’s delivery from the flag was perfect for Pearson but the defender headed wide of Pope’s goal.
More pressure from Brodie led to Pope putting the ball out for a Town throw and Devitt looked to work an opening from it, before Naylor also tried to find a way through but neither could get a shot in.
A foul by Artus on Cambridge captain Kevin Roberts gave the away side a free kick on the right and it led to the opening goal. Dunk whipped a good delivery to the penalty spot and the unfortunate NAYLOR got his head to it and sent the ball past McKeown for an own goal.
A Town free kick for a foul on Brodie gave the Mariners a chance to reply but again, Pope came off his line to catch the ball from Hatton.
The game stopped for Dunk and midfielder Tom Shaw to receive treatment after both went down under challenges from Cool in quick succession.
Brodie won possession from the resulting drop ball after the striker decided to contest it and it was played through for Marshall to drill a shot wide from 18 yards.
Brodie was involved again on 33 minutes as he burst into the penalty area but the Crawley loanee was unable to find the space to shoot and Thomas sent the ball out of play with a chipped cross from the left side of the box.
Elliott won a corner off Artus for Cambridge two minutes later but Dunk’s delivery was headed clear by Hatton. Town broke through Brodie and he looked to square the ball to Hatton inside the box but a vital interception saw it through to Pope. His clearance landed at the feet of Cook, whose long-range shot was blocked.
Town looked to be on top but were struggling to find an end product in front of goal, with Pope relatively untroubled so far.
A corner to the visitors initially caused some danger as McKeown failed to collect it but the keeper was there to make an excellent block from defender Josh Coulson.
The Mariners were on the attack again soon afterwards as Brodie beat the offside trap to get onto Cook’s pass on the edge of the area but he could not make it count, instead firing over the bar.
Two added minutes were played at the end of the half and Town were unable to create any further opportunities before the referee’s half-time whistle blew.
The hosts had played the better football for most of the half but had lacked the cutting edge needed to convert their good build-up play into goals.
That meant they would have to come from behind after the break, as Naylor’s own goal remained the difference between the two sides at the interval.
No changes were made before the restart and a foul by Pearson on Elliott gave Cambridge the first opportunity to create some danger. The free kick was flicked away by Naylor before Shaw sliced a shot out for a throw-in.
A long ball downfield from McKeown was flicked through and eventually nodded down by Cook for Brodie but his shot was stopped by Pope.
The visitors were on top in the early stages of the half though and they could have doubled their lead seven minutes in when Liam Hughes played a low ball across the six-yard box that Elliott only had to get a toe to but the striker could not stretch enough to divert it into the net.
Cambridge were picking up most of the loose balls in midfield and were posing a greater threat in attack.
That almost changed when Naylor ran onto a through-ball and chipped a first-time effort over the advancing Pope but the shot lacked direction and bounced wide.
The Town management team made their move on 65 minutes, replacing Marshall with Cook and sending Hearn on to a huge ovation from the home supporters in place of Brodie.
Hearn was fouled on the left to give the Mariners a free kick three minutes later but Colbeck’s flat delivery was poor and was headed clear.
A shot from Pearson was blocked for a corner soon afterwards but the home side were unable to create anything from it.
Cambridge were still looking dangerous in attack and they perhaps should have had a second goal when the ball deflected through to Shaw on the edge of the box. The midfielder prodded his shot past McKeown but saw it roll past the far post.
Colbeck won another corner at the other end on 71 minutes and this time, his delivery was better but again, Pope came off his line to claim the catch.
Another chance came when Shaw played the ball across the box for Dunk but his first-time shot was comfortable for McKeown.
A home penalty shout came when Devitt went down under a challenge inside the box but the referee waved play on, with few complaints from the Town players.
Grimsby won a corner when a diving header by Naylor from Colbeck’s driven cross was blocked but again, they were unable to create significant danger from the flag.
Artus was booked for a foul on Dunk as the winger looked to go clear down the right and from the free kick, Elliott headed over the bar.
Town’s next attack saw Colbeck lay the ball off for Artus 25 yards out but again, pope was untroubled as the ball flew over his crossbar.
Hearn tried a shot after chasing a ball down on the edge of the box, although he too missed the target.
Time was beginning to run out for the Mariners as the clock ticked past the 80-minute mark.
A further blow came when Pearson went down injured and limped off to be replaced by Wilson, who came on for his Town debut.
Colbeck did well to win a corner on the right with three minutes to go but his flag-kick was headed away and Elliott eventually broke, although Miller got back to challenge him.
That proved to be Elliott’s last action of the game as he was replaced by Nathan Blissett as the game moved into four added minutes.
Town were given a final chance to salvage something from the game with a free kick 25 yards out and Devitt’s shot was pushed over the bar for a corner by Pope.
That led to another corner but this time, as Pope pushed the ball away, the referee’s whistle brought the game to an end.
The result means Town are now ten points behind league leaders Mansfield ahead of Tuesday’s trip to Nuneaton..