The Mariners will return from Essex with all three points – thanks to an inspired Charles Vernam's first hattrick.
Town boss Ian Holloway made five changes going into the game, with Elliot Hewitt, Ludvig Öhman, Bradley Garmston, James Tilley and Matt Green coming into the starting line-up.
Town's back three were Waterfall, Öhman and Glennon, Hewitt and Garmston the wingbacks, with Benson and Whitehouse in the centre of the park, and Vernam and Tilley either side of Matt Green in the Mariners' attack.
The home side took the lead on 17 minutes when a great strike from Prosser flew past a stranded James McKeown from just inside the box.
But the Mariners were level minutes later when man of the moment, Charles Vernam, tucked away his third goal in four games.
It looked to be heading into the break all square, but the hosts had other ideas. The Mariners failed to clear a corner with the ball falling to a United attacker, his effort was well saved by McKeown but the Town stopper could do nothing to prevent Robinson mopping up.
Half Time: Colchester United 2-1 Grimsby Town
Town started the second half well and got a deserved equaliser on 66 minutes. A great cross from the right by Hewitt eventually found its way to Vernam lurking at the far post, with the Town frontman squeezing the ball past Gerken in the U's goal.
Three minutes later, who else, Charles Vernam grabbed Town's third at his third goal of the game. And what a goal it was. Town won the ball on the edge of their own box, Whitehouse fed Vernam, who was halfway inside his own half, the number 18 ran and ran, beating four players along the way, before firing the ball past Gerken and into the bottom right-hand corner.
What a comeback from the Mighty Mariners.
Another fantastic performance by Town and that man Charles Vernam.
Action & Reaction coming up.
The Mariners are next in action on Saturday when Morecambe are the visitors to Blundell Park.
United: Gerken, Jackson, Bramall, Prosser, Pell, Robinson, Comley, Harriott, Eastman, Stevenson, Nouble.
Subs: Ross, Sowunmi, Senior, Norris, Clampin, Gambin, Poku.
Town: McKeown (c), Hewitt, Waterfall, Öhman, Glennon, Garmston, Benson, Whitehouse, Tilley, Vernam, Green.
Subs: Russell, Pollock, Hendrie, Clarke, Grandin, Wright, Hanson.
Attendance: 2,954 (279)
Referee: Will Finnie
Possession: United 46%-54% Town
Next Up: Morecambe (H)