The 44-year-old took charge of Fuerth in 2009 and steered them to promotion last season, when they reached the Bundesliga for the first time in their history.
But they have won just twice in 22 games in the top flight, and sit bottom of the table with just 12 points to their name.
Saturday's 1-0 defeat at Fortuna Duesseldorf was the final straw for the board.
"We didn't come to this decision easily. Everyone knows what Mike Bueskens means to this club. Without him we wouldn't be in the Bundesliga," said Fuerth president Helmut Hack in a press conference.
"The fact is we only have 12 points, we wanted to create a stimulus so we could turn this around."
The club's Under-23 coach Ludwig Preis will take charge for Sunday's home game against Bayer Leverkusen, but Fuerth are hunting for a permanent solution -- whether or not they avoid relegation.
"We are looking intensively for a coach. He won't be someone just brought in to fight fires," said Hack.
"Because we have to plan for two possible outcomes, we need someone who fits with us, even in the case of relegation."
Fuerth's shock 2-1 victory at Schalke at the start of the month gave Bueskens -- a former Schalke player -- some brief respite, but it was their first win since beating Mainz 1-0 at the end of August.
Bueskens is the fourth coach to lose his job in the Bundesliga this season after Wolfsburg sacked Felix Magath in October, then, in December, Hoffenheim relieved Markus Babbel of his duties and Schalke fired Huub Stevens.
