Milito, who took charge in May and as a centre back helped Independiente win their last league title in 2002, is the 15th coach to leave a club in Argentina's 30-team championship since the beginning of the season in August.
“I gave of my best but it didn’t work out. I think this is the time to step aside,” the 36-year-old, younger brother of former Inter Milan and Racing Club striker Diego Milito, told reporters.
Independiente were jeered and whistled off the Estadio Libertadores de America pitch by fans angered by insipid performances in a poor recent run which had delivered two wins in their last seven matches.
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They go into the summer break with 22 points from 14 matches, including six wins.
Independiente, who lifted the last of their record seven crowns in the elite South American Copa Libertadores 32 years ago, last won a title in the second-string Copa Sudamericana in 2010.
(Reporting by Luis Ampuero; Writing by Rex Gowar; Editing by Toby Davis)
