'Gladbach are seven points from safety at the foot of the table and 46-year-old Frontzeck, who has been in charge for 18 months, was shown the door after his side have won just 14 of their 56 league matches under him.
While the defeat to St Pauli was the nail in his coffin, 'Gladbach allowed a 2-0 lead at home to Stuttgart slip to a 3-2 defeat the week before.
"After the two defeats against our main rivals, Stuttgart and St Pauli, we have had to consider our situation. This was a difficult decision," said 'Gladbach's director of sport Max Eberl.
"We wish we could have achieved all our goals with Michael Frontzeck.
"After our recent results, we decided to change our coach."
Frontzeck's successor has not been named, but former Tottenham Hotspur and VfB Stuttgart coach Christian Gross has been in talks with the club, according to reports.