This is the latest in a string of sackings sweeping through the Bundesliga, with seven coaches having parted company with German league teams this season.
The 42-year-old's final game in charge of Kaiserslautern was on Sunday at home to high-flying Schalke 04. They were beaten 4-1, their 17th consecutive match without a win.
"After the defeat to Schalke and lots of intense discussions, we have come to a group decision that we have to take this step," said Kaiserslautern chairman Stefan Kuntz.
"In the past few weeks and months, we have tried many different measures to get the team back on track. Unfortunately, none have been successful."
A new coach should be appointed soon, but assistant coach Oliver Schäfer and goalkeeping coach Gerald Ehrmann have already been installed as interim coaches for Saturday's match at Freiburg, who are 16th in the table.
Hertha Berlin coach Markus Babbel and manager Michael Skibbe were both sacked this season, while Marcus Sorg, coach at SC Freiburg, Michael Oenning, manager of Hamburger SV and Holger Stanislawski, 1899 Hoffenheim's manager were all also sacked by their respective teams.
But most recently, Cologne parted company with director of sport Volker Finke in early March.
Schalke 04 lost their manager Ralf Rangnick in September to ill health, as he was suffering from a burn-out.