Happy Harriers knocked out their high-flying National League visitors thanks to a second half penalty by Ashley Hemmings.
Watched by their biggest crowd so far this season - 2,799 - boss Russ Penn’s glory seekers were rewarded for their winning performance with prize-money worth £22,629.
Kidderminster, whose only previous FA Cup encounter against Grimsby was in 2012 when they won 4-2 in an away fourth qualifying round tie, made one change from the side which triumphed 4-0 in a National League North clash with Spennymoor Town seven days earlier.
Defender Geraldo Bajrami, sidelined through suspension for being sent off in a recent 1-1 league draw at Chorley, was replaced by Keith Lowe.
Academy defender Luke Bastable was named among the substitutes.
Harriers, buoyed by notching nine goals in their previous two Aggborough outings, gave their former Football League rivals a fright in the opening minutes when Amari Morgan-Smith had a header well saved by goalkeeper Max Crocombe.
The chance came after captain Sam Austin had robbed Giles Coke and set up the opportunity for Hemmings to send over a pin-point cross which found Morgan-Smith in space in front of goal.
The Aggborough striker had another chance shortly afterwards, but this time he powered his half volley into the side netting.
Grimsby responded with an excellent cross field ball by Ryley Towler which reached Michee Efete who created the opening for Will Bapaga to fire in a shot which was smartly saved by goalkeeper Luke Simpson.
The lively pace of the game continued with Ben Fox having a long range deflected shot safely gathered by Simpson.
Harriers, who triumphed over Sporting Khalsa, Ware and Bedfont Sports in the qualifying rounds, conceded the first corner of the game in the 52nd minute, but Seb Revan’s kick came to nothing.
Shortly afterwards the Mariners forced another corner and this time it resulted in Luke Waterfall firing wide from close range.
Grimsby went close on 65 minutes when substitute Lennell John-Lewis was denied by a fine save by Simpson before Efete a strong drive rebound off the inside of the near post.
Harriers, however, sealed a hard earned victory on 71 minutes when Hemmings calmly sent Crocombe the wrong way from the penalty spot after Waterfall had fouled substitute Ethan Freemantle inside the area.
It was his seventh goal of the season.
Kidderminster: Simpson; Penny, Cameron, Lowe, Richards; Hemmings (Martin, 79), Carrington, Bonds, Austin, Sterling; Morgan-Smith (Freemantle, 64). Subs not used: Emery, Bell, Lissimore, White, Bastable.
Grimsby: Crocombe; Efete, Waterfall (Grant, 73), Longe-King, Revan; Coke, Towler; Bapaga (John-Lewis, 59), Fox, Clifton; Taylor. Subs not used: McKeown, Pearson, Sears, Khouri, Braithwaite, Essel.
Referee: Gareth Rhodes.
Attendance 2,799 (921 away fans).