Goals from Andre Schuerrle, Nikolce Noveski and Sami Allagui moved Mainz on to 30 points from 14 games, with Dortmund hosting bottom team Borussia Moenchengladbach on Saturday.
After losing three matches in a row, surprise package Mainz have now won their last two league games to regain the momentum they built up after winning a record-equalling seven games at the start of the season.
"It was clear this would not be an easy game and that is the way it turned out," said Mainz coach Thomas Tuchel on a freezing evening with the pitch covered in a thin layer of snow.
"But we stayed patient and compact, although the 3-0 does not really reflect the game and it is a bit too high," said the league's youngest manager at 37.
Mainz did not have many chances in an evenly balanced first half but they caught Nuremberg's defence napping when Schuerrle tapped in from close range in the 27th minute for the lead.
Nuremberg went close again when Jense Hegeler's header hit the bar in the 72nd before Mainz sealed the win as Allagui was picked out by goalkeeper Christian Wetklo.
