"After a meeting (with directors) Eduardo Berizzo announced his time at Estudiantes was over and handed in his resignation," the club said on their website.
The team, winners of the Apertura championship in the first half of the 2010/11 season, are 15th in the Clausura with 19 points from 15 matches. The red and whites are 11 points off the pace after losing 2-0 at home to Independiente at the weekend.
The 2009 South American champions, with midfield general Juan Sebastian Veron missing through illness, were also knocked out of this year's Libertadores Cup in the first knockout round.
Estudiantes look set for a first win in 13 games in all competitions on Thursday when they play the remaining hour of the match played 10 days ago at relegation-threatened Huracan.
The red and whites were leading 2-0 when the game was abandoned in the 32nd minute due to crowd violence.
Former Argentina defender Berizzo, who was right-hand man to former Chile boss Marcelo Bielsa, began his first job as head coach in February when Alex Sabella surprisingly resigned a week before the start of the Clausura.
Estudiantes started well under Berizzo, winning five of their opening seven Clausura matches, but lost form soon after a 5-0 hiding by Cruzeiro of Brazil in their opening group match of the Libertadores Cup.
The team have been left rudderless since captain Veron decided two weeks ago to have surgery on a nagging heel problem in order to recover in time for next season.
Berizzo is the seventh first division coach to have quit or been sacked during the Clausura after Miguel Angel Brindisi at Huracan, Leonardo Madelon at Quilmes, Fernando Gamboa at Colon, Roberto Sensini at Newell's Old Boys, Ramon Diaz at San Lorenzo and Angel Cappa at Gimnasia-La Plata.
