A second-half brace for Per Nilsson was enough to earn the Bavarians victory after Mainz missed a penalty in the first half, while Nicolai Muller scored the visitors' consolation on the hour mark.
The win also lifts Nuremberg into the chase for a place in Europe next season, even if their coach Michael Wiesinger did not want to hear anything of that prospect on the eve of the game.
However, his side's sixth home win of the season may convince Wiesinger to alter that outlook with six games of the season remaining.
Mainz controlled proceedings throughout the first half, creating the better chances and wasted an ideal opportunity to take the lead in the 28th minute when Adam Szalai sent a penalty wide after Javier Pinola had fouled Muller.
Towards the conclusion of the first half, the Hungarian forward missed another opportunity as the home side just managed to go into the interval on level terms.
Wiesinger seemingly had some wise words for his side during the break as Nuremberg emerged with the same 11 players, but a different attitude.
Less than 10 minutes had been played when Hiroshi Kiyotake's free-kick was met by the head of Nilsson, who guided the ball into the left-hand corner.
A mistake by Raphael Schafer, who got a rush of blood to the head as he stormed out of his goal in the 60th minute, allowed Muller to bring Mainz level as he lobbed the ball astutely over the Nuremberg goalkeeper.
However, Nuremberg took the lead again in the 69th minute with Nilsson bundled the ball over the line after Kiyotake's corner was flicked on to the far post by Hanno Balitsch.
This time, they successfully defended their advantage, playing down the clock to close in to a single point of their opponents, four points away from the top six and a place in Europe next season while 14 clear of the relegation zone.