Nintendo of America marketing boss Cammie Dunaway will leave the games industry on October 1, the company's announced.
No reason has been given for the departure as yet.
"We appreciate Cammie's contributions to Nintendo and the role she played in bringing the Wii and Nintendo DS experiences to millions of people," said NoA head Reggie Fils-Aime.
"Her team and the rest of Nintendo of America remain focused on our goal of maintaining the incredible momentum Nintendo enjoys heading into the busy holiday season."
"I'm thankful for my time with Nintendo and proud of our team's accomplishments in growing the Nintendo audience," Dunaway added. "I look forward to watching the continued growth of the Nintendo brand in the years ahead."
Dunaway has been a visible element to Nintendo's American push, and has appeared on stage alongside NoA president Reggie Fils-Aime at several E3 press conferences.
She was the CMO for Yahoo! before joining Nintendo in 2007, replacing Fils-Aime in the role after he was promoted to his current position.
Dunaway has previously been named as one of the 100 top marketers by Advertising Age Magazine.
The news comes as Wii looks set to take a second place in the US this year to a surging Xbox 360.
Media Create figures also confirmed in the past week that PS3 has now passed Wii in Japan for the year.
Nintendo is set to announce a price and date for 3DS in Japan on September 29.