Howard (5-7, 3-5 Mid-Eastern Athletic) was down 26-7 midway through the third after Hampton's Christopher Dukes scored his second touchdown from 2 yards out.
The Pirates (3-9, 2-6) appeared to be riding the momentum that led them to a 40-35 upset of nationally ranked Bethune-Cookman the previous week.
But the Bison began a stampede to the end zone, scoring three straight TDs - Greg McGhee scoring from the 24, and Aquaniu Freeman on runs from the 2 and the 6, grabbing a 27-26 lead with 7:04 to play.
Hampton rallied for the lead one last time when Anthony Prevost kicked a 25-yard field goal with 3:38 to play.
Howard's final drive covered 71 yards in a grinding 13 plays before Fleck hit the winner.