Schalke 04 continued their recovery from a disastrous start to the season when they beat Darmstadt 3-1 on an eventful afternoon for Eric Maxim Choupo-Moting who set up one goal, scored another and missed a penalty.
Ibisevic, 32, reached his milestone on his 240th Bundesliga appearance, playing for his fourth club.
He scored his first six goals for Alemannia Aachen in 2006/07, then hit 43 goals in four seasons with Hoffenheim and 33 goals in four seasons with VfB Stuttgart.
The Bosnian has added another 18 for Hertha since joining them last season.
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Mainz went ahead in the 25th minute when Aaron Seydel, 20, scored on his Bundesliga debut but Ibisevic levelled with a shot on the turn from former Chelsea and Feyenoord forward Salomon Kalou's pass.
Mainz had midfielder Jean-Philippe Gbamin sent off for a second bookable offence in the 62nd minute before Ibisevic scored the winner from close range in the 67th minute from another chance provided by Kalou, who headed the ball into his path.
Just seven minutes later, however, Ibisevic was given a second yellow card for a needless foul and sent off.
Hertha have 24 points, ahead of Eintracht Frankfurt on goal difference and six behind leaders RB Leipzig. Bayern Munich are second with 27.
Schalke extended their unbeaten record to 12 matches in all competitions, including seven in the Bundesliga.
After they lost their first five Bundesliga games of the season, Schalke's run has taken them up to eighth place with 17 points from 12 games.
Darmstadt, a lowly 15th, stunned the hosts when they took a sixth-minute lead from a move which started with a Schalke corner.
Sandro Sirigu collected the ball and burst down the right, then slipped the ball to Marcel Heller who rounded Ralf Faehrmann to score.
Sead Kolasinac equalised in the 26th minute, heading in from Choupo-Moting's cross.
The Cameroon forward had a chance to get on the scoresheet himself two minutes later when Schalke were awarded a penalty but Darmstadt goalkeeper Michael Esser saved the shot with his legs.
Choupo-Moting was not to be denied, however, and put Schalke ahead on the hour, poking home the ball from Max Meyer's cross.
Alessandro Schoepf sealed Schalke's win with a third goal in the final minute.
(Writing by Brian Homewood in Berne; Editing by Clare Fallon)
