After three quarters of play, the Bulldogs found themselves down 24-12 but scored twice in the fourth quarter to tie the game.
Their first score of the fourth came after recovering a NMCC fumble which led to an 8-yard run by Sikeston's Reece Porter with 3:19 left to play.
Within the last minute, Sikeston quarterback Colton Hampton hit Corbyn Blissett from 20 yards out to tie the game at 24-24.
After being granted a rare overtime period, Sikeston made the most of it.
The Bulldogs converted a huge fourth and six play when Marquez Newman worked for just enough on a screen pass to get the first down.
Porter finished their game-winning drive with a 3-yard run to give the Bulldogs their first lead of the night as well as the win.
"This is the second week in a row that we've fallen back and then had to come back," Sikeston coach Alan Scheeter said. "It was a good game and I'm definitely proud of them.
"We got to see a lot of our young guys and they got a lot of game experience."
NMCC took an early 12-0 lead after the first quarter following a 6-yard touchdown pass and a 15-yard run.
Porter put the Bulldogs on the board in the second quarter with his first of his three touchdown runs on the night.
The Eagles began the third quarter with a 14-yard run to go up 18-6, but Newman rushed for a 48-yard touchdown nearly 30 seconds later to cut NMCC's lead to six once again.
NMCC pushed their advantage back to two touchdowns following a 6-yard run with 1:50 left in the third quarter.
Sikeston (2-0) will travel to Farmington on Monday to take on the Knights for their next contest.