The 20-year-old loan striker from Blackburn doubled his tally for the season to give the hosts just their fourth home win of the season.
Clarke struck in the tenth, 59th and 84th minutes, although Mariners front-man Adam Proudlock had equalised just a minute short of the quarter hour mark.
Both sides are still languishing at the wrong end of League Two but three points give Stanley some much needed breathing space after their horrendous run.
Speedy Clarke opened the scoring early when he converted a neat Chris King cross from close range.
But no sooner had the home fans finished celebrating, Grimsby were level through Proudlock, the former Wolves striker, who fired home into the bottom right corner from inside the box.
Both sides were cagey for the rest of the first half, and early in the second, before Clarke latched onto a Phil Edwards ball just before the hour mark to slot home into the bottom left corner.
And the Londoner completed his first ever career hat-trick six minutes from time when he controlled goalkeeper Ian Dunbavin's long punt forward to again convert into the bottom left corner from inside the box.
While Grimsby will leave East Lancashire safe in the knowledge that they still have a healthy cushion over the teams in the drop-zone, while Accrington are finally moving in the right direction.