Mainz took the honours in the Rhine-Main derby to edge towards the top six and dent Eintracht Frankfurt's own European hopes with a 3-1 win at the Waldstadion.
Goals from Andreas Ivanschitz and Shawn Parker gave Thomas Tuchel's side a two-goal cushion to take into the interval and a third from Nikolce Noveski ended Frankfurt's hopes early in the second half.
An Adam Szalai own goal was a gift to the home side in the 55th minute but Frankfurt did nothing with it, nor did they capitalise on playing the last two minutes against 10 men after Julian Baumgartlinger was sent off.
Mainz have been the top side in the region ever since condemning their local rivals to relegation in 2011, but this season's form had indicated that Frankfurt wanted that berth back.
It did not look that way after 18 minutes, though, when Mainz stunned the Waldstadion - which had remained silent for the first 12 minutes as part of a league-wide protest against new security proposals.
Ivanschitz, who has been criticised by his coach for not scoring enough goals lately, put the visitors in front as he exchanged passes with Parker before beating Kevin Trapp.
The first test of Christian Wetklo in the Mainz goal came from his own player a minute later when Bo Svensson looped the ball up toward his own goal, but the Mainz custodian saved his blushes.
Parker, given a rare start by Tuchel, was clearly motivated to take his chance and, after sending a speculative effort over the bar, he slotted in Mainz's second in the 42nd minute after latching on to Eugen Polanski's through-ball.
The game was decided in the 52nd minute when Nicolai Muller's corner was met by the unmarked Noveski, who headed in the visitors' third.
Szalai gifted Frankfurt a route back into the game just three minutes later when he diverted Takashi Inui's cross into his own goal.
Frankfurt were unable to build on that goal, though, and never put Mainz under any serious pressure.
Mainz again shot themselves in the foot with Baumgartlinger picking up a second yellow card in the 88th minute but even with 10 men, they held on to their lead.