"It's with great sadness that I write to say that I have relieved Gennaro Gattuso of his duties as first-team manager," Zamparini wrote on the club's official website.
"Unfortunately for both me and him, we might have bitten off a little bit too much for his first experience as manager, at a club with a demanding public like Palermo's. Results have shown that we were wrong (to offer Gattuso the job)."
Gattuso, a former Italy international and AC Milan midfielder who arrived from Sion in June after a disappointing time as player-coach last season, was fired by the trigger-happy Zamparini after losing 2-1 at Bari on Tuesday.
Palermo, relegated from Serie A last season, are languishing in 12th place after winning two of their opening six games.
The club said Gattuso would be replaced by Giuseppe Iachini, who managed Siena last season until leaving after they too were relegated to Serie B.
Zamparini, nicknamed the 'manager eater' is famous for firing coaches and this sacking marks the 52nd time he has relieved a manager of their duties.
Last season, he used three different coaches, two of them twice. He fired Gian Piero Gasperini, replaced him with Alberto Malesani for three games, then brought back Gasperini before sacking him after two matches. He eventually returned to Giuseppe Sannino, who had started the season as manager but was sacked after three matches.