The 44-year-old became the fourth coaching victim in nine rounds of matches in the Clausura championship and the second of the weekend.
One of the longest-serving coaches in the always tense, results-first atmosphere of the Argentine domestic game, Sensini been in charge since 2009 - an eternity in a country where coaches rarely last more than a few months at a club.
"Despite trying to convince him to carry on, he's a man of the house and we must respect his decision," sporting director Gustavo Dezotti said on the club's official website.
"He decided to go because the last thing he wants is to harm Newell's," added Dezotti, a former team mate of Sensini's at the club and in Argentina's 1990 World Cup final side.
"It's a decision he'd been thinking about for some time and perhaps he took time to make it because of our relationship and because we insisted he stay despite the series of negative results."
Newell's 2-0 defeat by Velez Sarsfield on Sunday was their fourth in five matches and seventh game without a win.
Sensini leaves Newell's, the club where he began his playing career in 1986, one from bottom of the standings with five points.
There is no fear of relegation, though, with their three-season points average much healthier.
Sensini spent the better part of his playing career in Italy with Udinese, Parma, where he won the UEFA Cup in 1999, and Lazio, where he won the Serie A title in 2000.
He played for Argentina at three World Cups and retired at Udinese aged 39.
Newell's are away to bottom side Quilmes on Friday.
Fernando Gamboa, another former Newell's player, was sacked by Colon at the weekend with his team in mid-table on 13 points but having lost four successive home games.
