The Argentine side, twice Libertadores runners-up, were beaten 3-1 by Colombia's Atletico Nacional in Rosario in their final Group Six match on Thursday.
They had lost the city derby 1-0 at home to Rosario Central on Sunday and also gone down 1-0 at River Plate in Buenos Aires in their previous league match.
"Today my link with Newell's ends," Berti told a news conference at the club's Marcelo Bielsa stadium on Friday.
"Given that this run of results wasn't good, I've decided to step aside," said Berti, who leaves Newell's in 14th place in the Final championship, second in the season, with 14 points from 12 matches.
"Unfortunately a cycle has ended in the way we least wished," said club president Guillermo Llorente.
Newell's, who boast Argentina World Cup players Maxi Rodriguez and Ever Banega, won last season's Final championship and reached the Libertadores Cup semi-finals under Martino before he left to take charge of Barcelona.
Atletico Nacional, South American champions in 1989, will meet holders Atletico Mineiro of Brazil in the last 16.
- Sports & Recreation
- Atletico Nacional
- Rosario Central
- Marcelo Bielsa