Norbert Haug will leave his role as Mercedes motorsport chief at the end of 2012 after 22 years in the role.
The 60-year-old German oversaw Mercedes' return to Formula 1 in 1994, initially as an engine supplier with Sauber and then McLaren.
Mercedes returned as a full constructor in 2010 when the manufacturer bought the then world champion Brawn team.
In his time in charge Mercedes-powered drivers and teams have won 87 grands prix and a total of six world titles.
"I would like to thank the best car company in the world for more than 22 years, which never had a single moment without passion for me," Haug said.
"I particularly wish to thank the board for the trust and freedom they have always given me with all my activities.
"Since 1991, we had tremendous achievements and wins, for which I want to thank all of my colleagues.
"Unfortunately, with one victory in 2012 since founding our own Formula 1 works team in 2010, we couldn't fulfil our own expectations.
"However, we have taken the right steps to be successful in the future. Our team and our drivers will do everything to achieve these goals."
Dieter Zetsche, CEO of Mercedes owner Daimler, paid tribute to Haug's commitment over the past 22 years.
"Norbert Haug was the face of the Mercedes-Benz Motorsport programme for more than 20 years," he said.
"For me, he put his stamp on a whole era and, as a highlight, he was responsible for the successful comeback of the Silver Arrows to Formula 1.
"In the name of the board of management and the whole motorsport family, I would like to thank Norbert for his extraordinary commitment to the three-pointed star."
Mercedes DTM driver Gary Paffett said he was sorry Haug was leaving.
"Sad to see a man that has done so much for me move on," he wrote on Twitter.
Haug has not revealed what he plans to do following his Mercedes departure.