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.
Haug in numbers
1990 - The year in which Haug became Mercedes motorsport vice-president. He joined on October 1, just days before Jean-Louis Schlesser and Mauro Baldi clinched the World Sportscar title in a Mercedes C11
986 - Total number of races featuring a factory Mercedes presence during the Haug era. The three-pointed star won 439 of them, or 45 per cent if you prefer.
500 - Mercedes built an engine with the aim specifically to win the Indianapolis 500, and achieved it in 1994 with Penske and Al Unser Jr, breaking its Indycar series duck in the process. Eighteen more victories followed, with Unser and Greg Moore recording five of them each.
87 - Number of Formula 1 wins taken by Mercedes-powered cars during the Haug era. Mika Hakkinen took all 20 of his grand prix wins and his 1998-99 titles in McLaren-Mercedes. Lewis Hamilton in 2008 and Jenson Button in 2009 followed with McLaren and Brawn. The three-pointed star also powered cars to two constructors' titles.
19 - total number of DTM titles won, nine drivers' crowns courtesy of Klaus Ludwig, Bernd Schneider, Gary Paffett and Paul di Resta and 10 constructors' prizes.
13 - Drivers' titles won in major Formula 3 championships since Mercedes' engine programme began during the last decade. Jamie Green won the first in the Euro Series in 2004, while Lewis Hamilton, Paul di Resta, Nico Hulkenberg, Romain Grosjean and Jaime Alguersuari followed. A total of 189 major F3 wins have been scored, including 10 at the Masters and four at Macau.
10 - Mercedes won all 10 races of the 1998 FIA GT Championship; Ludwig and Ricardo Zonta taking the drivers' title ahead of '97 champion Bernd Schneider and Mark Webber.
2 - Championships won in the short-lived DTM successor, the ITC. Schneider again took the drivers' crown while a squad including Dario Franchitti.
1 - Number of grand prix wins gained by Mercedes as a constructor since returning to F1 in 2010. Nico Rosberg scored the victory at this year's Chinese Grand Prix.