Grimsby took an early lead through Sam Jones’ header to shock the hosts.
The away side then doubled their lead in the second half, through an own goal by Callum Kennedy and capped off the three points with a third through substitute Scott Vernon.
Leyton Orient nearly conceded in the opening minute, as Charlie Grainger was charged down by Callum Dyson but the block was eventually pounced on by Charlie Grainger.
Danny Webb named an unchanged eleven after their enthatic 4-0 away victory at bottom of the table Newport County last week. Although Michael Clark, Nigel Atangana and Rowan Liburd returned to the bench, as Paul McCallum and Sammy Moore were out with knee injuries.
The visitors took the lead to stun the O’s just six minutes in, as Danny Andrew’s was allowed to whip a ball in for Jones to head in at the far post.
Michael Collins’ almost threaded a great ball through for Josh Koroma but his run was just too early, as he was given offside.
In injury time of the first half Dominic Vose, went for goal from a dangerous free-kick on the edge of the box which bounced up infront of Grainger who pushed it passed the post.
In the second half, Grimsby again looked threatening when inside the Orient half. This time a cross was half cleared to Jones who went for an audacious overhead kick which went wide of the target.
Grimbsy burst through the vacant Orient defence, as Jones attacked the box cut inside Myles Judd but Hunt’s last minute challenge denied the away side an almost certain second goal.
The vistors nearly extended their advantage, as Andrew was slotted into the box but he fired over.
Grimsby doubled their lead shortly after, as Jones close range shot from inside the six-yard box was superbly saved initially by Grainger but rebounded back off Kennedy into the net.
Orient nearly got themselves back into the game, as Koroma found some space on the edge of the box and hit a snap shot which went just over the bar.
Koroma again went on his own when he picked the ball up outside the box and wriggled around the defence but his shot hit the side netting.
Grimsby then rounded off the match with two minutes of time, as the ball was lifted over the O’s defence for substitute Vernon to guide his volley into the top corner and seal the three points for the away side.
Kennedy almost got a late consolation in injury time for the O’s, as his strike on the break rattled the post – as the O’s remain second from bottom.
Leyton Orient Lineup: 12 Charlie Grainger, 29 Myles Judd, 16 Nicky Hunt (C), 6 Tom Parkes, 3 Callum Kennedy, 23 Freddy Moncur, 7 Michael Collins, 31 Steven Alzate, 28 Josh Koroma, 22 Sandro Semedo, 30 Sam Dalby (70)
Substitutes: 24 Sam Sargeant, 34 Michael Clark, 19 Teddy Mezague, 32 Henry Ochieng, 15 Nigel Atangana, 35 Tristan Abrahams (70), 20 Rowan Liburd
Grimsby Lineup: 1 James McKeown, 5 Shaun Pearson, 22 Danny Collins, 3 Danny Andrew, 12 Zac Mills, 18 Tom Bolarinwa (56), 8 Craig Disley, 26 Brandon Comley, 10 Dominic Vose, 35 Sam Jones (82), 29 Callum Dyson (65)
Substitutes: 2 Ben Davies, 20 Andrew Boyce, 21 Scott Vernon (82), 27 Adi Yussuf, 32 Jamie Osbourne (56), 33 Akwasi Asante (65), 34 Luke Maxwell
Attendance: 5,688 (1,086)