The promoted club have won just twice all season and are currently 14 points from safety.
Buskens, who guided the team to the second division title last season, will be replaced by Under-23 coach Ludwig Preis and sporting director Rouven Schroder on a temporary basis.
"We know what we have to thank Mike Buskens for, so it was a decision that was very difficult for us," said club president Helmut Hack in a statement.
"We still have a chance to stay up. Therefore, we want to try to give the team a new impetus."
Greuther Furth go into this Sunday's clash with Bayer Leverkusen four points behind 18th-placed Hoffenheim in the relegation playoff place.