"This has been an amazing and incredibly fulfilling journey, filled with challenge, an overwhelming passion for the brand, and many special people," de Nysschen wrote in the e-mail.
"These have truly been the best years of my life, and I know the best years for Audi still lie ahead. It is a magnificent company, a magnificent brand and I shall watch the continued progress of the four rings with interest and envy."
De Nysschen's departure is unrelated to reports of a management shake-up at Audi's parent, Volkswagen AG, Stertz said.
"It was an opportunity that he found attractive," Stertz said. "It was his decision. It wasn't forced on him."
Stertz said he did not know where de Nysschen was headed.
De Nysschen has been Audi of America's president for seven years, leading the brand as its share of the luxury market climbed to 9.5 percent in 2011 from 5.3 percent in 2004. Audi today said its May U.S. sales rose 10 percent to 11,503 -- the brand's best performance ever in the month of May.