Spokes' second-half stunner came in a game that was largely devoid of clear cut chances and gave the Lincolnshire side their first victory in over a month.
Rob Kelly's team were left frustrated on a night where they struggled to get going all evening and saw their winning run of four matches come to an end.
Story of the match
Both sides came into the game having seen a recent upturn in form but still in desperate need of points to get them clear of the relegation zone, and it was the bottom of the table visitors who made the more attacking start following the kick-off.
Harry Clifton coming close to giving Grimsby the lead when he got on the end of a James Hanson flick-on before seeing his looping effort dip just over the bar in the 14th minute.
Paul Hurst's side then again threatened after 24 minutes when Lenell John-Lewis turned Barrow defender James Jones on the edge of the box and produced a thunderous strike which flew over the goal by just inches.
The hosts, who came into the match following their best run of form of the season thus far, struggled to get a hold of the game in the first half, coming closest to scoring themselves in the 42nd minute when a curling free-kick from Oliver Banks created a scramble in the box before being well taken care of by the Grimsby defence.
The game began to open up following the break, however, with the Bluebirds producing quick passing move out wide before Chris Taylor played the ball into Scott Quigley who fired just over from 20 yards with 55 minutes gone.
It proved to be the visitors though who would take the lead not long after when John-Lewis held up the ball in the box before laying off to Luke Spokes who produced a magical strike to beat goalkeeper Joel Dixon and curl into the top corner from 25 yards out.
Rob Kelly's team then looked to produce a quick response to Spokes' wonder-goal, creating a chance in the 78th minute when Mariners number one James McKeown fumbled catching a deep corner from Taylor, creating a back post scramble from which the Cumbrian side failed to convert.
Barrow further piled on the pressure in the games dying moments, coming close to an equalizer after 85 minutes when Quigley managed to get in behind the defence before seeing his driven shot just tipped over by McKeown from a tight angle.
Quigley then again came close to snatching a point for his side at the death when he received a flick on in the box from substitute Calvin Andrew but saw his close-range shot again well saved by the Town goalkeeper.
The three points see Grimsby remain in bottom place but close the gap on their opponents, who sit one place above the drop zone, to seven points.
Man of the match - Luke Spokes
In a relegation six-pointer that is always likely to be devoid of quality, one piece of magic can often be all that separates the sides, and that is what Spokes produced.
His second-half stunner, the 20-year-olds first goal of the season, was a goal that will, without doubt, live long in the memory for any Mariners supporter.
This fixture was a must-win for Paul Hurst's team and Spokes goal has just about kept their hopes of survival alive.