Zimling put Thomas Tuchel's men in front in the 64th minute with Muller scoring his second goal in two games moments later.
Sebastian Freis gave Freiburg some hope with an almost immediate reply, but the visitors held on for victory as the hosts searched in vain for an equaliser, leaving gaps which Mainz very nearly exploited.
The opening exchanges were tactical as both sides appeared to be waiting for the other to take the first gamble and after a first half bereft of chances, it was Mainz who seized the initiative.
Not long after Eric-Maxim Choupo-Moting was brought on as an additional striker, the visitors took the lead with Zimling heading Johannes Geis' cross in from the edge of the six-yard box.
Choupo-Moting missed the chance to make it 2-0 soon afterwards when he was denied by Oliver Baumann after going clean through on goal.
But Zimling then teed up Muller to ensure Mainz doubled their lead with a shot from a tight angle into the far corner.
Freiburg threw caution to the wind and pulled a goal back through Freis, who was put through by Gelson Fernandes and kept his cool to make it 2-1.
Mike Hanke saw a good chance go begging to equalise before Yunus Malli missed the chance to restore Mainz's two-goal lead.
Choupo-Moting and Muller both missed the target in the closing stages for Mainz as they comfortably held on for victory.