The former Netherlands international was appointed on a three-year contract at the start of June.
Wolfsburg started the 2021/2022 campaign on a high, winning their first four Bundesliga games but that remains their only wins of the season so far.
Wolfsburg are winless in their last eight games across all competitions and have lost their last four Bundesliga games, including last Saturday's 2-0 home loss to Freiburg.
The Bundesliga outfit are also bottom of their UEFA Champions League group which has Lille, Salzburg and Sevilla.
Sporting director Jorg Schmadtke said: “The bottom line was that there were more dividing than connecting factors.
“The conviction to get out of the difficult sporting situation in this constellation and to bring about the U-turn as soon as possible was missing and made us decide to end the cooperation.”
Upon his departure, Van Bommel added: “I am surprised and disappointed with the decision because I am convinced that together we would have managed to get back on the road to success.
“I wish the team that they quickly manage to turn things around again.”
Van Bommel previously managed PSV Eindhoven in his homeland but was sacked after 18 months.
The 44-year-old played in Germany for Bayern Munich, winning two Bundesliga titles with the Bavarians.
Van Bommel had two spells at PSV as a player, winning four league titles and also had a stint at Barcelona, where he won La Liga and the 2006 Champions League.
He became Bayern Munich's first ever non-German captain and won two Bundesliga titles in Bavaria.
Michael Frontzeck has been placed in interim charge of Wolfsburg until a new manager is appointed.
