"Mike Mack has informed the board of his intention to step down as chief executive officer and executive director of the company," Syngenta said in a statement, adding that Mack would leave by the end of next week.
He will be replaced temporarily at the helm by the company's finance chief John Ramsay, it said.
"I believe that this is an appropriate time for the company to benefit from the perspectives of a new leader," said Mack, a US citizen who has worked for Syngenta for the past 14 years — eight of them as company chief.
His departure comes after American seed giant Monsanto in late August finally dropped its campaign to buy Syngenta for some $46 billion.
That sent the Swiss company's share price into a tailspin, and it has lost more than 20 percent of its value over the past two months.
In a move to placate shareholders, the company last month announced it would sell its vegetable seed business and buy back $2 billion worth in shares in a bid to "accelerate shareholder value creation".
But last weekend, a group of shareholders got together to demand a revision of Syngenta's strategy, slamming the company among other things for missing a range of value-creating opportunities in recent years.
The market meanwhile welcomed Wednesday's announcement, allowing Syngenta's
share price to shoot up more than six percent to 18.80 francs apiece in midday trading as the Swiss stock exchange's main SMI index shed 0.03 percent.